GUIDELINE for Feline Herpesvirus infection
Last updated: 08/06/2022
The feline herpesvirus infection guidelines were first published in J Feline Med Surg 2009; 11: 547-555 and updated in J Feline Med Surg 2013; 15: 531-533 and in J Feline Med Surg 2015; 17: 570-582; the present guidelines were updated by Corine Boucraut-Baralon and Etienne Thiry.
- The domestic cat is the main host of feline herpesvirus (FHV) although other felids can be infected.
- Prevalence of infection is high especially in large populations and in shelters.
- FHV infection causes acute upper respiratory and ocular disease, which is particularly severe in young kittens. Corneal dendritic ulcers are considered a pathognomonic manifestation of FHV ocular infection.
- Following the acute phase of the disease, almost all cats undergo a latent infection, which can lead to recurrent clinical signs, mainly ocular diseases (conjunctivitis and keratitis) after intermittent reactivation. However, reactivation can also be asymptomatic.
- The preferred method to detect FHV in biological samples is PCR and taking samples at different sites (e.g. conjunctival, oro-pharyngeal and nasal swabs) significantly increases the detection rate.
- Trifluridine (topical) and Famciclovir (systemic treatment) are the preferred antiviral drugs for treatment of acute FHV ocular diseases, but other antiviral drugs are available.
- Cellular immunity plays an important role in protection against the disease and antibody testing is not useful to predict protection.
- FHV vaccine is considered as a core vaccine. Only modified live and inactivated parenteral vaccines are available and there is no difference in efficacy regarding the disease. All the vaccines are combined with FCV.
- Maternal antibodies interfere with the response to vaccination until eight weeks of age on average. Two vaccinations at an interval of two to four weeks are generally recommended for primary vaccination, irrespective of the vaccine type. After the first annual booster, three-years interval boosters should preferentially be given when the risk of infection is considered as low. In shelters or high-risk situations, annual boosters can be considered.
The agent of the feline viral rhinotracheitis is distributed worldwide and belongs to the order Herpesvirales, family Herpesviridae, subfamily Alphaherpesvirinae, genus Varicellovirus. The new (actual) name of this virus is Felid alphaherpesvirus-1 (however for practical purposes, it is named FHV all along this guidelines). Another feline herpesvirus belonging to the Gammaherpesvirinae subfamily of Herpesviridae (FcaGHV1: Felid Gammaherpesvirus 1) and described in cats (Troyer et al., 2014) is not related to FHV. Although only one serotype is described for FHV, the virulence can differ between viral strains (Gaskell et al., 2007); differences can also be observed by restriction endonuclease analysis (Hamano et al., 2004; Thiry, 2006). However, a recent molecular study failed to correlate viral genomic polymorphisms and severity of clinical signs (Lewin et al., 2020).
The genomic double-stranded DNA of FHV is packaged into an icosahedral capsid surrounded by a proteinaceous tegument and a phospholipid envelope, which contains at least ten glycoproteins.
 Serotype: antigenic property allowing different strains to be distinguished by serological methods. Serotype should be differentiated from genotype, which refers to characterization by molecular methods.
In the feline host, FHV replicates in epithelial cells of the conjunctiva, cornea and the upper respiratory tract, and in neurons. The neuronal infection enables the virus to establish lifelong latency after primary infection. FHV is related antigenically to canine herpesvirus and phocid (seal) herpesviruses 1 and 2; there is no known cross-species transfer (Gaskell et al., 2006).
The virus is inactivated within 3 hours at 37°C and is susceptible to most commercial disinfectants, antiseptics and detergents. At 4°C, it remains infectious for about five months, at 25°C for about one month, and it is inactivated at 56°C in 4-5 minutes (Pedersen, 1987).
The domestic cat is the main host of FHV, but FHV has been isolated also from other felids, including cheetahs and lions, and antibodies have been detected in pumas (Carmel et al., 2017; Chaber et al., 2017; Witte et al., 2017). Clinical signs have been described after infection in wild felids, including dermatitis in cheetahs. Cheetahs especially are very sensitive to FHV, including development of serious clinical signs after being vaccinated with modified-live vaccines (Pennings et al., 2020).
In healthy small populations, the prevalence of viral shedding is usually less than 10% of cats, whereas in large populations, especially those containing cats with visible clinical signs, up to 50% can shed virus (Coutts et al., 1994; Binns et al., 2000; Zapirain et al., 2004; Helps et al., 2005; Berger et al., 2015; Fernandez et al., 2017). The highest positivity rates (25 to 50%) are generally observed when cats with acute upper respiratory tract disease (URTD) are sampled (Schulz et al., 2015; Fernandez et al., 2017; Zirofsky et al., 2018).
The results of prevalence studies depend on the diagnostic method used to diagnose FHV infection; PCR detection of FHV DNA is more sensitive than virus isolation, which was the technique used in many older studies. One multicentric Spanish study, exploring the prevalence of different pathogens in healthy and diseased cats by PCR, found that FHV was detected in 6% of healthy cats, 28% of cats with URTD and 24% of cats with conjunctivitis (Fernandez et al., 2017). In another study in Switzerland, 9% of asymptomatic cats tested positive for FHV by PCR (Berger et al., 2015). In shelters, the risk is higher, and with increasing time spent at a shelter facility, the rate of shedding increases: 4% of cats are shedders upon entering the shelter and after one week this increases, with 50% of the cats shedding (Pedersen et al., 2004). The low initial prevalence of shedding likely reflects the intermittent nature of viral excretion during latency, while the high rates after one week are likely due to both new infections in naïve cats and reactivation in latently infected cats.
Following infection via the nasal, oral or conjunctival route and after the acute phase of the disease, FHV frequently develops latent chronic infection, similarly to many other herpesviruses. During chronic infection, intermittent reactivation may occur, which gives rise to the re-activation of viral shedding in oronasal and conjunctival secretions. Except in catteries with more densely housed multiple cats, contamination of the environment does not generally play a role in transmission. During latency, virus is not shed, but virus shedding by acutely infected cats, as well as by latently infected cats experiencing reactivation, are the two main sources of infection (Gaskell and Povey, 1982).
Transplacental infection has not been described in the field. Latently infected queens can however transmit FHV to their offspring because parturition and lactation are stressful events that can lead to viral reactivation and shedding. Kittens can therefore acquire FHV infection at an early age. The outcome of infection depends on the presence of maternal-derived antibodies (MDA): when high levels are present, kittens are protected against disease and experience subclinical infection that leads to virus latency, whereas in the absence of sufficient MDA, clinical manifestations of infection can follow (Gaskell and Povey, 1982).
The virus enters the body via the nasal, oral or conjunctival routes. It causes a lytic infection of the nasal epithelium with spread to the conjunctival sac, pharynx, trachea, bronchi and bronchioles. Lesions are characterised by multifocal necrosis of epithelium, with neutrophil granulocyte infiltration and inflammation. In one study, a transient viraemia associated with blood mononuclear cells was observed after natural infection in young cats (Westermeyer et al., 2009). This has been observed exceptionally also in neonates (Gaskell et al., 2007).
Viral shedding or excretion starts as soon as 24 hours after infection and lasts for one to three weeks. Clinical signs usually appear two to six days after experimental infection depending on the infectious dose of virus (Gaskell and Povey, 1979) but the incubation period can be longer. Acute disease usually resolves within 10 to 14 days (Westermeyer et al., 2009) although ocular signs, in cases of keratitis, can persist longer (Nassise et al., 1989). Some animals develop chronic lesions in the upper respiratory tract and in ocular tissues.
Following infection, the virus spreads along the sensory nerves and reaches the neurons, particularly in the trigeminal ganglia, which are the main sites of FHV latency. It is thought that all cats experiencing primary infection are likely to become lifelong latent carriers. There is a correlation between severity of clinical signs and quantity of viral DNA in the trigeminal ganglia (Townsend et al., 2013). There are no direct diagnostic methods to identify latency because the virus persists as genomic DNA in the nucleus of the latently infected neurons, without replication or shedding. Virus shedding can however be induced experimentally in approximately 70% of latently infected cats following glucocorticoid treatment. Other reactivating stressful events include lactation (40%) and moving the cat into a new environment (18%) (Gaskell and Povey, 1977; Ellis, 1981; Gaskell and Povey, 1982; Pedersen et al., 2004).
Some adult cats show acute clinical signs at the time of viral reactivation; the disease resulting from such reactivation is referred to as recrudescence. Reactivation without clinical signs is also observed (Povey and Johnson, 1970; Gaskell, 1974).
Viral replication is associated with conjunctivitis, ulcerative keratitis and rhinotracheitis. In advanced stages of disease corneal neovascularization can be associated to a stromal keratitis related to immune-complexes deposition, and scarring. In case of degeneration of the stroma a corneal sequestrum occurs. The pathomechanisms of corneal damages have been shown by experimental infections (Nasisse et al., 1989; Maggs, 2005). Eosinophilic keratitis has also been linked to the presence of FHV in the cornea and/or blood (Nasisse et al., 1998). However, a definite causal association was not confirmed, since some affected cats are FHV negative (Cullen et al., 2005). Viral DNA has been detected in the aqueous humour of a larger proportion of cats suffering from uveitis as compared to healthy cats (Maggs et al., 1999b).
Periocular and facial ulcerative dermatitis are also reported (Holland et al., 2006). Damage to the nasal turbinates during acute disease is thought to be a predisposing factor for chronic rhinitis (Gaskell et al., 2007).
Chronic rhinosinusitis, a frequent cause of sneezing and nasal discharge, has also been associated with FHV infection; however, viral DNA is detected only in some cats affected by chronic rhinosinusitis, and also in healthy controls (Henderson et al., 2004). Additionally, FHV replication is not observed and possibly the virus initiates the condition and it is then maintained by immune-mediated mechanisms with inflammation and remodeling phenomena leading to a permanent destruction of nasal turbinates and bone, and complicated by secondary bacterial infection (Johnson et al., 2005).
Co-infection with FCV is common, particularly in young kittens and histopathological lesions in the lungs suggest that FHV-induced damage to airways and impaired immune response can facilitate secondary infection and development of FCV-specific lesions (Monne Rodriguez et al., 2018). FHV infection often occurs in combination also with Chlamydia felis, Bordetella bronchiseptica, Mycoplasma spp. and various other bacteria, including Staphylococcus spp. and Escherichia coli, can lead to secondary infection of the respiratory tract, causing a multi-agent respiratory syndrome (Gaskell et al., 2006).
Abortion is a rare secondary effect, which is not a direct consequence of viral replication in contrast to herpesvirus infections in other species (Hoover and Griesemer, 1971).
In general, during their first weeks of life, kittens are protected against infectious diseases by MDA. However, it is important to note that during FHV infection, the MDA levels are generally low and this may influence the outcome of the infection. MDA can persist for a maximum of 10 weeks (Johnson and Povey, 1985), but in some cats have vanished already at 6 weeks of age (in about 25% of kittens; Dawson et al., 2001); in another study, 37% of kittens still had detectable antibodies at the time of the 8-weeks vaccination (DiGangi et al., 2011). The level of MDA is variable from one litter to another and even between kittens from the same litter (Poulet, 2007).
Glycoproteins embedded in the FHV envelope are important inducing immunity; after infection, the detection of virus neutralizing antibodies (VNA) correlates with the recognition of FHV glycoproteins (Burgener and Maes, 1988). Immunisation of rabbits with the FHV membrane protein glycoprotein D led to the production of high VNA titres (Spatz et al., 1994).
Natural FHV infection does not result in comprehensive immunity; in general, the immune response protects against disease but not against infection. After re-infection, mild clinical signs have been observed only 150 days after primary infection (Gaskell and Povey, 1977). VNA titres after natural infection are often low and rise slowly – indeed they can still be absent after 40 days (Gaskell and Povey, 1979). VNA most likely contribute to the protection against acute infection.
However, many adult cats do not have VNA despite previous vaccination and/or do not respond to revaccination by a four-fold increase in VNA titres (Bergmann et al., 2020). Conversely, a study that used a quantitative ELISA antibody test in a cohort of 100 client-owned cats showed a higher titer of antibodies (Munks et al., 2017).
Other antibody-mediated mechanisms, e.g. antibody mediated cellular cytotoxicity (ADCC) and antibody-induced complement lysis, have been demonstrated (Wardley et al., 1976).
As in other alphaherpesvirus infections, cell-mediated immunity plays an important role in protection, since the absence of antibodies in vaccinated cats does not mean that cats will develop disease: after one vaccination with either inactivated or modified live vaccine, cats do not develop protective antibody titres until after 14 days (Lappin, 2012) and most seropositive cats (i.e. presence of VNA) are protected against FHV virus challenge, although one third of seronegative cats are also protected (Lappin et al., 2002).
The relative efficacy of vaccination with a modified live vaccine against viral challenge in 8-9 months old cats was similar after 1 week or 4 weeks post vaccination in another study confirming the onset of protection within one week (Jas et al., 2009). Younger cats (5 months old) can also overcome challenge only 7 days after one vaccination with either an inactivated or a modified-live vaccine (Summers et al., 2017).
On the other hand, vaccinated cats challenged 7.5 years after vaccination developed fewer clinical signs (relative efficacy of 52%) suggesting long term immunity preventing acute disease but not local mild infection or shedding (Scott and Geissinger, 1999). Detectable antibodies can persist for more than 3 years but, in some cats, persistence of antibodies after vaccination can be shorter (Scott and Geissinger, 1999).
Although the presence of antibodies and protection against clinical signs are correlated (19 seropositive cats among 21 were protected against a virus challenge, Lappin et al., 2002), there is currently no test available that predicts the degree of protection in individual cats.
Since FHV is a pathogen of the respiratory tract, mucosal, cellular and humoral responses are important. Studies with intranasal vaccines have shown clinical benefits as early as 2-6 days after vaccination (Slater and York, 1976; Weigler et al., 1997b; Lappin et al., 2006). A study using deleted mutant virus administered first by SC route and then intranasal route three weeks later showed better protection against clinical signs, nasal shedding and development of lung and turbinate lesions after challenge, compared to a commercial licensed modified-live vaccine, suggesting that mucosal immunity is important for better protection (Lee et al., 2021) as was suggested in previous studies with intranasal vaccines (Lappin et al., 2006; Reagan et al., 2014).
Moreover, non-specific protective mucosal immunity was induced by LTC (liposome toll-like receptor ligand complexes), reducing the severity of clinical signs and viral loads in a controlled study in kittens (Contreras et al., 2019).
FHV infection typically causes acute upper respiratory and ocular disease, which is particularly severe in young kittens. Viral replication causes erosion and ulceration of mucosal surfaces, resulting in rhinitis, conjunctivitis, and occasionally corneal ulcerative disease. FHV is the most important cause of corneal ulceration (Hartley, 2010) with dendritic ulcers considered a pathognomonic manifestation (Maggs, 2005). However, small punctate ulcers can be seen or larger geographic ulcerations can develop (Gould, 2011).
Typical clinical signs of FHV infection start with salivation, sneezing, followed by pyrexia, depression and anorexia, serous or sero-sanguineous ocular and/or nasal discharge, and conjunctival hyperaemia (Gaskell et al., 2006). Secondary bacterial infection is common, in which case discharges become purulent. Occasionally, primary pneumonia and a viraemic state are seen, with severe generalized signs and a fatal outcome (Gaskell et al., 2006). Co-infection with feline calicivirus (FCV) is common, particularly in young kittens, and histopathological lesions in the lungs suggest that FHV-induced damage to airways and impaired immune response can facilitate secondary infection and development of FCV-specific lesions (Monne Rodriguez et al., 2018).
Less frequently, oral ulceration, dermatitis, skin ulcers are observed (Hargis and Ginn, 1999). A case of erythema potentially related to FHV infection and associated with facial erosive-ulcerative dermatitis has been described (De Lucia et al., 2021). Association with neurological signs is very rare but has been observed after experimental infection (Gaskell et al., 2006).
Abortion is a rare consequence of FHV infection in cats, and when it occurs it is not due to viral replication in the foetus but is secondary to the general disease pathogenesis, in contrast to herpesvirus infections in other species (Hoover and Griesemer, 1971).
FHV was not associated with feline chronic gingivostomatitis (FCGS) in two controlled studies (Belgard et al., 2010; Nakanishi et al., 2019) that tested for FHV, FCV, FIV, Chlamydia felis, Bordetella spp. and Bartonella henselae. In these two studies, only FCV prevalence was significantly higher in the FCGS group compared to the control group.
After reactivation and recrudescence of infection, cats can show upper respiratory and ocular disease, as described above. Others present with chronic ocular immune-mediated disease in response to the presence of FHV antigen. This pathogenic mechanism has been suggested in experimental infections resulting in stromal keratitis with corneal oedema, inflammatory cell infiltrates, vascularisation and eventually blindness (Nasisse et al., 1989; Maggs, 2005). A preliminary controlled clinical and post-mortem trial found abnormalities in FHV antibody positive cats (corneal hypoesthesia and tear film deficiencies) suggestive of corneal innervation damages more frequently compared to naïve individuals (Sebbag et al., 2021).
Table 1. FHV disease, lesions and clinical signs
|Disease type||Pathology||Main clinical manifestations|
|Classical acute disease(≤10 days in duration)
|Rhinitis, conjunctivitis, tracheitis, superficial and deep corneal ulcers (can include dendritic ulcers which are pathognomonic for FHV if they are seen; Gould, 2011)||Sneezing, nasal discharge, salivation, coughing, conjunctival hyperaemia and serous ocular discharge|
|Atypical acute disease||Peri-ocular and facial dermatitis
|Nasal and facial ulcerated and crust-forming lesions
Severe systemic signs, coughing, death (acute death in kittens, “fading kitten syndrome”)
|Chronic disease (immune-mediated disease)||Stromal keratitis
|Corneal oedema, vascularisation, blindness
Chronic sneezing and nasal discharge
*Exclusion of concurrent infection with other agents is required to determine the FHV aetiology of chronic rhinitis
Fig. 7. Skin ulceration in the course of an FHV infection. ©Dr. Jacques Fontaine (Uccle, Belgium)
Diagnostic imaging (may be performed in chronic rhinitis cases)
In case of chronic rhinitis and obstructive respiratory syndrome diagnostic imaging investigations are needed to differentiate inflammatory and neoplastic diseases. They include radiography and computed tomography of the head, followed by nasal endoscopy. All these techniques are performed under general anesthesia. Both radiography (performed with appropriate projections) and computed tomography (CT) provide information about the involvement of nasal turbinates and septum, frontal sinuses, nasopharynx and tympanic bullae. However, the turbinate structure and the extent of mass lesions are more effectively evaluated by computed tomography scans and additionally the integrity of the cribriform plate can be assessed (Reed and Gunn-Moore, 2012). Radiography can reveal turbinate or vomer bone destruction, asymmetry of the nasal cavity and increased soft tissue density in the nasal cavity or sinuses. Computed tomography (CT) allows for further evaluation of the nasal cavity, sinuses, and middle ear to demonstrate possible turbinate or vomer destruction, bullae opacification and soft tissue opacity within the nasal cavity or sinuses.
Endoscopic evaluation of the nasopharynx and sample collection (swabs, aspirates, flushes, and biopsies) are performed under general anesthesia after radiography or CT scan, as they are invasive techniques and cause changes that interfere with the interpretation of images.
Rhinoscopy can be performed in chronic rhinitis cases under general anesthesia.
Severe abnormalities can be seen in both neoplastic and inflammatory chronic nasal disease with turbinate and paranasal bone lysis and medial retropharyngeal lymphadenopathy among others. Despite unilateral lesions are more frequently observed in neoplasia, nasal biopsy is recommended to confirm diagnosis (Lamb et al., 2003; Schoenborn et al., 2003; Tronblee et al., 2006; Nemanic et al., 2015).
Detection of the infectious agent
Detection of FHV is possible by viral isolation, detection of antigen by immunofluorescence or detection of viral genomic DNA by PCR.
Virus isolation (VI) has been used for diagnosing FHV infection for many years and indicates the presence of viable virus, not just DNA.
In cats undergoing primary FHV infection, the virus can be detected by VI from conjunctival, nasal or pharyngeal swabs or scrapings, or from post-mortem lung samples. VI has good sensitivity in acute disease, but samples must be collected before the ocular application of fluorescein or Rose Bengal stain, which inhibits viral replication in cell culture (Brooks et al., 1994; Storey et al., 2002). Also, clinical specimens for VI should be put into viral transport medium, sent quickly to the laboratory, and refrigerated during shipping, in order to preserve viability of the virus. The swabs are inoculated onto feline cell cultures where the presence of FHV is identified by a characteristic cytopathic effect. VI is becoming less common as diagnostic laboratories switch to PCR-based methods.
Antigen detection by immunofluorescence
FHV-specific antigen can be detected by immunofluorescence assay (IFA) on conjunctival or corneal smears or biopsy specimens. As for VI, the use of fluorescein staining should be avoided before sampling, as it can give false-positive results and make test interpretation difficult. IFA is less sensitive than VI or PCR (Nasisse et al., 1993; Burgesser et al., 1999). Because of its low sensitivity and the interference with fluorescein, which is often used in ophthalmology practice, IFA is not the most suitable diagnostic test in chronic ocular disease (Nasisse et al., 1993) and is no longer routinely available.
Polymerase Chain Reaction (PCR)
The preferred method to detect FHV in biological samples is PCR performed in a diagnostic laboratory test for the presence of FHV DNA in the sample.
The PCR assays currently used can detect FHV DNA in conjunctival, corneal or oropharyngeal swabs, corneal scrapings, aqueous humour, corneal sequestra, blood or biopsy specimens. Conventional PCR, nested PCR and, more recently, real-time quantitative PCR have all been used (Hara et al., 1996; Nasisse and Weigler, 1997; Stiles et al., 1997a, 1997b; Weigler et al., 1997a; Maggs et al., 1999a; Sykes et al., 2001; Vögtlin et al., 2002; Helps et al., 2003; Marsilio et al., 2004; Litster et al., 2015a). Most PCR primers and probes are based on the highly conserved thymidine kinase gene of the viral genome. Real-time PCR is the most frequently used method for routine diagnostics because of its high sensitivity, specificity and the possibility of obtaining quantitative results regarding the amount of FHV DNA present in the sample, which can be easier to interpret in a clinical context.
Molecular diagnostic methods such as PCR are more sensitive than VI and indirect immunofluorescence methods that detect FHV antigen (e.g. in conjunctival swabs) (Reubel et al., 1993; Stiles et al., 1997b; Weigler et al., 1997a; Burgesser et al., 1999; Litster et al., 2015a). The sensitivity of PCR depends on the test format (Maggs and Clarke, 2005) and PCR should include controls to test for the absence of PCR inhibitors and the quality of the sample.
A positive qualitative PCR result could indicate just low-level shedding, especially in scrapings of the cornea and/or tonsils (Reubel et al., 1993; Stiles et al., 1997a; Maggs et al., 1999b) and does not mean that the virus is responsible for the observed clinical signs, although it indicates the possibility of recurring signs in the future. However, when quantitative real-time PCR is used (Vögtlin et al., 2002), the amount of viral DNA measured can provide additional information on the aetiological importance of the agent: high viral DNA loads in nasal secretions, oro-pharyngeal swab or tears suggest active replication and involvement of the virus in acute clinical signs. In contrast, low viral DNA loads in corneal scrapings would indicate only asymptomatic shedding or chronic infection. Interpretation of positive results can also depend on the population tested e.g. shelter cats are more likely to test positive than household cats.
In cats with URTD, the oropharynx is the preferred single sampling site for the detection of FHV, if only one sample can be taken; however, taking samples at additional sites (e.g. conjunctival and nasal swabs) significantly increases the detection rate. Interestingly, sampling from a site with URTD-associated lesions did not increase the likelihood of detection in one study (Schulz et al., 2015).
Additionally, PCR tests can detect FHV DNA in modified-live virus (MLV) vaccines (Maggs and Clarke, 2005). However, there are few published data reporting PCR results in cats in the days/weeks after vaccination with MLV vaccines. In a study in which eight cats were vaccinated with a MLV vaccine, no FHV DNA was detected in the 7 days following vaccination (Summers et al., 2017). Lee et al. (2021) did not detect FHV DNA in nasal swabs of vaccinated cats after the first or the second vaccine injection three weeks later with a commercial MLV vaccine. This suggests that even recent vaccination with a MLV vaccine does not interfere with PCR diagnostics in diseased cats.
When considering molecular diagnosis in clinical practice, fluorescein and topical anaesthetics should not be used before contacting the diagnostic laboratory because these compounds might affect PCR sensitivity, depending on the method used (Gould, 2011; Segarra et al., 2011). It is also advisable to contact the diagnostic laboratory in advance for details of sample collection and shipping, which is mostly done with regular mail at ambient temperature (Maggs, 2005). Using the same sample, PCR allows the simultaneous detection of other feline pathogens frequently implicated in respiratory and ocular diseases, especially Chlamydia felis, Feline Calicivirus, Mycoplasma felis or Bordetella bronchiseptica (Helps et al., 2003, 2005; Marsilio et al., 2004; Litster et al., 2015a; Schulz et al., 2015; Fernandez et al., 2017).
Other molecular methods, sometimes presented as PCR methodology but which in fact use non-PCR technology (e.g. isothermal amplification) have been developed (Liu et al., 2019; Tan et al., 2020); these methods can be used as point-of-care tests in the clinic but very few have been validated for routine use. These methods use lysis of the sample instead of nucleic acid extraction; for this reason, they are easier to perform and can be done in the clinic with a result obtained in less than one hour. ABCD does not recommend use of these methods until they have been validated for diagnostic purposes in independent studies.
Antibodies to FHV can be detected by a neutralization test or ELISA in serum, aqueous humour and cerebrospinal fluid samples (Dawson et al., 1998; Maggs et al., 1999b). Due to natural infection and vaccination, many cats have antibodies and the demonstration of specific antibodies consequently does not correlate with disease and active infection (Maggs et al., 1999b).
Moreover, antibody detection does not allow differentiation between infected and vaccinated animals. Neutralizing antibodies are undetectable until 20 to 30 days after primary infection, and antibody titres are commonly low, both in animals with acute and latent infection. Consequently, antibody detection is of limited value in the diagnosis of FHV infection (Nasisse and Weigler, 1997; Maggs et al., 1999b; Maggs, 2005).
Regarding prevaccination testing, CMI is more important for protection, but the cellular immune responses can only be measured by more sophisticated laboratory methods (Thiry et al., 2009), and serum antibody testing is also not useful to predict protection (Bergmann et al., 2020). Therefore, ABCD does not recommend use of prevaccination testing for FHV vaccination (see also the ABCD guidelines “Vaccination and antibody testing”).
A review has been published by Bergmann et al. (2019).
Cats severely affected by FHV infection need intensive nursing care and supportive therapy. The resolution of dehydration and restoration of electrolytes and the acid-base balance (e.g. replacement of losses of potassium and bicarbonate due to salivation and reduced food intake), preferably by intravenous administration, is required in cats with severe clinical signs. Food intake is extremely important. Many sick cats do not eat because of their loss of smell due to nasal congestion or sometimes because of ulcers in the oral cavity. Food can be blended to cause less pain when eating, should be highly palatable, and can be warmed up to increase the smell. Appetite stimulants (e.g. mirtazapine 1.88-2 mg/cat PO, SID if renal and hepatic function is not compromised, give EOD if it is) can be used. Alternatively, commercial fluid high-energy diets can be used for hand feeding. If the cat has not eaten for three days, placement of a nasal or oesophageal (or naso-oesophageal) feeding tube and enteral nutrition are indicated. Naso-oesophageal tube (NOT) placement usually requires no sedation but cats with FHV infection might resent the presence of the tube around the nose and sometimes intermittent placing of the NOT for each feed can work better than leaving one in place. Softer silicone tubes are now available that can be used for cats with soreness of the nose and/or pharynx. In more severe cases and in cats that are expected to eat within a few days, oesophagostomy tube feeding can be used; these need short general anaesthesia for placement but allow for medicating and easier feeding via the wider bore tubes which are away from the cat’s face.
For cats with severe nasal congestion, cheap small nebulisers (Fig. 8) can be purchased for use in the veterinary clinic (or loaned to owners to use at home) for regular nebulisation therapy with saline (q 4-6 hours if possible for 15 mins at a time) – in the hospital setting this can be applied close to the cat’s face by placing the cat in an igloo and covering the igloo for example. This can rehydrate the upper respiratory tract, loosen secretions, reduce congestion and increase comfort.
Fig. 8. Nebulisation therapy for cats with severe nasal congestion. ©The Feline Center, Bristol, UK
If a nebuliser is not available, an alternative is to provide steam therapy. Owners can do this at home by sitting with their cat with care in a bathroom with hot running water/shower. Adequate humidity will be present when the bathroom mirror becomes ‘foggy’ and the time this takes will depend on the size of the bathroom.
With nasal discharges, these should be cleaned away several times a day with physiological saline solution, and a barrier cream ointment can be applied locally to protect the skin around the nose. In some chronic cases, nasal flushing under general anaesthesia may be performed to dislodge severe congestion and discharge. If there is a mucous nasal discharge, drugs with mucolytic effects (e.g. bromhexine) may be helpful. Lubricant eye drops can be used several times a day.
Non-steroidal anti-inflammatory drugs can be used to decrease fever and oral pain, but only once dehydration is corrected, and ideally when there is food intake. Maropitant is sometimes used in cats with upper respiratory symptoms, but there is no study proving its efficacy in these conditions, and moreover there is no indication to use it in cats with FHV infection.
At the clinician’s discretion, antibiotics should be given to cats with severe disease and suspected secondary bacterial infection. An empirical choice is usually made initially, as diagnostic tests are unlikely to be indicated or performed in acute infection. It is crucial to use antibiotics with good penetration in the respiratory tract and/or oral cavity. Oral doxycycline (5-10 mg/kg q12 to 24h) for 7-10 days is recommended as a first line treatment in the ISCAID guidelines (Lappin et al., 2017). Alternatively, amoxicillin (20 mg/kg q8h) can be used unless infection with Chlamydia felis and/or Mycoplasma or Bordetella spp. has been evidenced, in which case doxycycline is preferred.
Other supportive treatments include Vitamins A, C, B12, but no scientific evidence exists for their efficacy.
Table 2. Symptomatic treatment for acute respiratory disease
|Drug||Comment||ABCD recommendation||EBM level|
|Nebulisation||To clean nasal discharge and to prevent dehydration of the upper airways||Nebulization is recommended several times daily.||4|
|Nasal flushing with nasal drops or physiological saline solution under GA||To clean nasal discharge and to prevent dehydration of the upper airways||recommended several times daily||4|
|Highly palatable food||To ensure sufficient food intake||Necessary, if cats do not eat because of pyrexia and/or ulcers in the oral cavity, or because of their loss of smell due to nasal congestion; food can be blended and warmed up to increase smell.||4|
|Placement of a feeding tube and enteral nutrition||To ensure sufficient food intake||Necessary if the cat has not been eating for three days or more||4|
|Local analgesia||To reduce local pain||Lidocaine 2% max 4 mg/kg + Chlorhexidine gel (10 mg/g of the gel)||4|
|Fluid therapy||To control dehydration and restore electrolyte and acid base imbalance||Necessary in cats with severe clinical signs||4|
|Antibiotics||To control secondary bacterial infections||Broad-spectrum antibiotics with good penetration in the respiratory tract are recommended for cats with severe disease – doxycycline, amoxicillin.||4|
|Non-steroidal anti- inflammatory drugs||To decrease fever||Recommended if cat is severely depressed – avoid if cat is dehydrated||4|
|Analgesic drugs||To reduce pain||Buprenorphine 0.01-0.04 mg/kg (every 6-8h), Metamizol (30-50 mg/kg) every 8h (not available in all countries)||4|
|Drugs with mucolytic effects (e.g., bromhexine)||To solve mucous nasal discharge||Might be helpful||4|
Table 3. Symptomatic treatment for acute ocular disease (conjunctivitis and keratitis)
|Drug||Comment||ABCD Recommendation||EBM Level|
|Antibiotics||To control secondary bacterial infections||Topical antibiotics||4|
|Anti-inflammatory drugs||To decrease local inflammation||Usually not needed; to avoid corticosteroids||4|
Table 4. Antiviral drugs recommended for topical and systemic treatment of acute FHV ocular disease.
The drugs are listed in decreasing order of preference. A review has been published in 2016 (Thomasy and Maggs, 2016).
|Drug||Type of drug||Route of administration||Efficacy in vitro||Efficacy in vivo||Controlled study in vivo?||Comments||EBM level|
|Trifluridine||Nucleoside analogue||Topical use
every hour for 1st day and every 4 hours thereafter (Maggs, 2001)
|Excellent||n.d.||No||Topical treatment of choice in ocular FHV manifestations. Some cats averse to topical application. Toxic if given systemically (Maggs, 2001)||3|
|Cidofovir||Nucleoside analogue||0.5% solution applied topically||Yes (cell cultures and corneal explant)||Yes||Yes||Topical treatment for ocular FHV; potent drug with only two daily applications (Fontenelle et al., 2008; Maggs, 2010)||3|
use initially ever 2-4 hours (Maggs, 2001)
|Excellent||n.d.||No||Topical treatment for ocular FHV. Difficult to source, pharmacists can formulate a 0.1% ophthalmic solution. Toxic if given systemically.||3|
|Ganciclovir||Nucleoside analogue||Topical||Excellent||Yes||n.d.||Topical treatment for ocular FHV. Good in vitro activity (Maggs and Clarke, 2004; van der Meulen et al., 2006).||3|
|Ganciclovir||Nucleoside analogue||0.15% gel q8h||Excellent||Yes||n.d.||Efficacy in vitro and well tolerated in vivo (Lewin et al., 2020b)|
|Aciclovir||Nucleoside analogue||Topical and oral||Poor
(high doses can be needed to overcome viral resistance)
|Some||Yes||Least in vitro effect of all herpes antivirals (van der Meulen et al., 2006; Williams et al., 2004), moderate in vivo effect (Williams et al., 2005). Synergy in combination with human IFN−α (Weiss, 1989). Toxic systematically (Maggs, 2001; Maggs, 2010)||3|
|Drug||Type of drug||Route of administration||Efficacy in vitro||Efficacy in vivo||Controlled study in vivo?||Comments||EBM level|
|Famciclovir||Nucleoside analogue (prodrug)||Oral, 90 mg/kg bid for 21 days||Yes (for penciclovir, as famciclovir is a prodrug of penciclovir)||Yes||Yes||Tested in conventional and SPF cats experimental challenge, against primary infection (Malik et al., 2009; Thomasy et al., 2011)||3|
|Famciclovir||Nucleoside analogue (prodrug)||Oral, 90 mg/kg bid 21 days||Yes||Yes||Placebo-controlled study in a shelter (Reinhard et al., 2020)||3|
|Famciclovir||Nucleoside analogue (prodrug)||Oral, 90 m/kg tid||Yes||No||Tested in a field study (59 cats showing ocular signs / dermatitis presumed FHV related) – Improvement of clinical signs, few side-effects, dose effect. (Thomasy et al., 2016)|
|Famciclovir||Nucleoside analogue (prodrug)||Oral, dose of 30 or 90 mg/kg bid 7 days||Placebo-controlled study Reduction of shedding at day 7 and day 15 whatever the dose (shelter) (Cooper et al., 2019)|
|Feline IFN-ω||Interferon||Systemic: 1 MU/kg SC sid or eod
Oral: 50,000 – 100,000 units daily
Topical: dilute 10MU vial in 19ml 0.9% NaCl and use as eye drops: 2 drops in each eye 5 times a day for 10 days (Jongh, 2004).
|Yes||n.d.||Yes||Safe and licensed for use in cats.
A combined topical and oral pre-treatment before experimental FHV infection was not beneficial (Haid et al., 2007).
|Human IFN-α||Interferon||SC high dose
PO low dose
|Yes||Yes||Yes||Less bioactive than feline interferon.
5-35 Units daily reduces clinical signs but not FHV shedding. Used along with l-lysine in chronic infections.
80 mg q12h 14 days
|Yes (cell culture and corneal explant model)
(Pennington et al., 2016)
|Some||Yes||Effect on duration of shedding and reduced clinical signs in an experimental infection (controlled – placebo study) (Spertus et al., 2019)||3|
n.d. = not determined; eod = every other day; sid = once daily; bid = twice daily; tid = three times daily.
The drugs listed might not be readily available or licensed for cats in all countries.
The amino acid l-lysine has been proposed for systemic treatment, to be administered as a bolus, separate from food. No side effects have been published, but there is no evidence of efficacy (Maggs, 2001, 2010; Stiles et al., 2002; Maggs et al., 2003, 2007; Rees and Lubinski, 2008; Drazenovich et al., 2009; Gould, 2011). Because of lack of efficacy, l-lysine supplementation is not recommended for preventing FHV re-excretion. Cave et al. (2014) investigated the effects of physiologic concentrations of l-lysine on the in vitro replication of FHV at L-arginine levels sufficient to maintain cell growth. FHV was not inhibited at any l-lysine concentration studied. Today there is no proof of any in vivo efficacy of l-lysine: an extensive review and comparison of the results of seven studies (including five studies in cats and two in vitro studies as well as studies in humans) has been published by Bol and Bunnik (2015). The conclusions of this meta-analysis of data taken all together is that lysine is not effective for prevention or treatment of the FHV infection. Moreover, although no negative effect on an adult cat’s health has yet been demonstrated, l-lysine supplementation might potentially impact a kitten’s growth by inducing arginine deficiency, as has been demonstrated in puppies (Czarnecki et al., 1985).
Other drugs have been proposed for the treatment of FHV ocular infections, including bromovinyldeoxyuridine, HPMA, ribavirin, valacyclovir, vidarabine, foscarnet and lactoferrin. However, the efficacy of these drugs has not be proven. Sinefungin, a nucleoside antibiotic showed inhibition of viral replication in vitro (Kuroda et al., 2019), but in vivo studies are lacking.
Association of low dose of Interleukin12 and interferon-gamma in long term treatment induced clinical improvement in FHV-infected cats in a placebo- controlled, double-blinded study (Fiorito et al., 2016).
Polyprenyl immunostimulant (PPI) has been used in a randomized blinded placebo-controlled study in experimentally infected cats and led to an improvement of clinical score in treated cats. Moreover, a safety study in 390 healthy cats did not show any side-effects of the oral administration of the therapeutic dose i.e. 0.5 mg/kg of PPI up to 14 days (Legendre et al., 2017). PPI is licensed for use against FHV-induced disease in USA. However, ABCD considers that independent field studies are needed before recommendation of this product.
A ramdomized controlled pilot study using probiotics (Enterococcus faecium SF68) or a placebo on 12 cats chronically infected with FHV was published several years ago but the very preliminary results suggest that supplemented cats have less morbidity associated to FHV infection (Lappin et al., 2009b). However, this has not been supported by further studies.
Alternative innovative therapies are under investigation. Sub-conjunctival injections of mesenchymal stem cells have been used with some efficacy (regression of corneal proliferation and decrease of neovascularization) against FHV-related chronic feline eosinophilic keratitis refractory to current treatment in a non-controlled study in five cats. Cytological examination of cornea did not reveal any eosinophils or mast cells at the end of the study and no local or systemic complications were observed during the study (Villatoro et al., 2018).
Prevention of reactivation
Use of a pheromone to prevent reactivation of FHV has been investigated in one randomized double-blind placebo-controlled study (twelve cats, 8-week study period) with neither significant effects on cortisol concentration nor viral detection, although some efficacy in reducing sneezing in the treated group was seen (Contreras et al., 2018). More data are needed to evaluate the use of pheromones to prevent reactivation.
General recommendations on vaccine type and vaccination protocol
FHV infection is common and can induce severe, even life-threatening disease. ABCD therefore recommends that all cats should be vaccinated against FHV. Vaccination provides protection against clinical signs and reduces viral shedding within one week of administration (Jas et al., 2009; Summers et al., 2017), but – as for other respiratory tract infections – it does not provide full protection from infection; 70 to 90% reduction in clinical scores has been achieved following experimental challenge soon after vaccination (Gaskell et al., 2007; Jas et al., 2009). In addition, vaccination can reduce field virus shedding (Gaskell et al., 2007; Lee et al., 2021) or duration of shedding (Jas et al., 2009). Even less protection is expected following vaccination under particular circumstances, such as with extremely high challenge doses or immunosuppression. Field strain variation does not play a role in protection provided by FHV vaccination.
Most current FHV vaccines are combined with FCV, either as bivalent products (only in some countries) or with additional infectious agents. Both modified live and inactivated parenteral vaccines are available. Subunit FHV vaccines and modified intranasal vaccines have been, or still are, available elsewhere in the world, but no longer in Europe.
For routine vaccination, there is no reason to choose any FHV vaccine above another, since all are based on a single serotype. Moreover, it has not been demonstrated that a MLV vaccine provides better protection against challenge 7 days after a single vaccination in 5 month-old kittens (Summers et al., 2017) than an inactivated vaccine.
For FHV, CMI is important for protection, however the cellular immune responses can only be measured by more sophisticated laboratory methods (Thiry et al., 2009), and serum antibody testing is also not useful to predict protection (Bergmann et al., 2020). Methodological issues can complicate comparison of titres (particularly when obtained from different laboratories), and they are no good predictors of FHV protection. Also, cats without any evidence of seroconversion have been found to be protected (Lappin et al., 2002; Mouzin et al., 2004). Vaccinated cats usually develop an anamnestic response upon field infection, although about 15% of cats can be non-responders (Mouzin et al., 2004).
Virulence genes deleted vaccines have been used for prevention of herpesvirus disease in cattle and pigs and show good efficacy in reducing clinical signs and respiratory shedding; FHV deleted mutants (Protein Kinase negative or gE and Thymidine Kinase negative) have been recently developed and tested in a challenge study in 4 month-old kittens (SC / intranasal vaccination protocol), demonstrating good safety after intranasal administration and better reduction of clinical signs, viral shedding, reduction of viral DNA in the trigeminal ganglia and reduction of occurrence of lesions compared to a commercial MLV vaccine (Lee et al., 2021).
Primary vaccination course
Maternal antibodies interfere with the response to vaccination until eight weeks of age on average (Poulet, 2007); the primary course of vaccination is therefore usually started at around nine weeks of age, although some products are licensed for earlier use, if the infection risk is high. Kittens should receive a second vaccination two to four weeks later, with the second given not less than twelve weeks of age. A first booster is recommended at the age of 10 to 16 months. This protocol has been developed to ensure optimal protection.
In contrast to live vaccines against feline parvovirus, where a single vaccination is efficacious for adult cats of unknown or uncertain vaccination status, for FHV two vaccinations at an interval of two to four weeks are recommended, irrespective of the vaccine type. However, in a recent study using two different FHV vaccines (one modified-live and one inactivated), a single vaccination resulted in significant reduction of clinical signs after challenge 7 days later in five month-old serologically negative kittens, suggesting that even a single vaccination can provide a quick level of protection useful in high-risk situations (Summers et al., 2017).
There are now several vaccines licensed for three years interval vaccination boosters. Protection against severe clinical signs for several years after vaccination has been demonstrated in challenge studies (Scott and Geissinger, 1999; Gore et al., 2006; Jas et al., 2015). For this reason, ABCD recommends that boosters should preferably be given at three years intervals to protect individual cats against field infections and to avoid potential adverse reactions (see also ABCD Guidelines ”Adverse reactions to vaccination”). However, an informed decision should be taken on the basis of a risk-benefit analysis and annual boosters can be considered in specific and high-risk situations, e.g., for shelters and boarding catteries or breeding catteries to protect young kittens in the first weeks of life (see below).
Experimental studies including challenge or antibody surveys in the field have clearly shown that immunity against FHV lasts longer than one year (Scott and Geissinger, 1999; Lappin et al., 2002; Mouzin et al., 2004). However, lack of seroconversion had been observed in some vaccinated cats (Lappin et al., 2009). On the other hand, all five month-old kittens seroconverted in the 28 days following challenge in another study (Summers et al., 2017). While most cats in the field either have antibodies against FCV and FPV, or show an anamnestic response after the booster, only 30 to 40% have antibodies against FHV, and 8 to 20% fail to react to booster vaccinations (Lappin et al., 2002; Mouzin et al., 2004; Bergmann et al., 2020). In the later study, pre-vaccination FHV neutralising antibody titres were present in 41% of cats not vaccinated during the last year (45/110) and titres were generally low (range 10-640). FHV antibody response to vaccination was observed in only 8% (9/109) of vaccinated cats. Cats ⩾2 years of age were more likely to have pre-vaccination neutralising antibodies than cats aged between 1 and 2 years. Cats from breeders were more likely to have pre-vaccination neutralising antibodies than privately owned cats. Domestic shorthair cats were more likely to show an at least four-fold titre increase after vaccination than purebred cats. Thus, many cats have no detectable neutralising antibodies against FHV despite previous vaccinations and fail to develop a ⩾four-fold titre increase after vaccination (Bergmann et al., 2020). Similar findings were also described in a previous study in which SPF-derived seronegative ten month-old cats were vaccinated once with a MLV vaccine and only 2 cats amongst 8 seroconverted (Lappin et al., 2009). Also, cats without any evidence of seroconversion have been found to be protected (Lappin et al., 2002; Mouzin et al., 2004). Vaccinated cats usually develop an anamnestic response upon field infection, although about 15% of cats can be non-responders (Mouzin et al., 2004).
All together it suggests that cellular immunity plays an important role in protection against the disease and that antibody testing is not useful to predict protection. Moreover, methodological issues can complicate comparison of titres (particularly when obtained from different laboratories).
In efficacy studies, protection clearly decreases with time. However, in a recent controlled study using a MLV vaccine, the efficacy of a three-yearly vaccination interval to reduce severe clinical signs was demonstrated after an experimental challenge and a long-lasting and stable humoral immune response has been observed (Jas et al., 2015).
If booster vaccinations have lapsed, a single injection is adequate if the interval since the last vaccination is less than three years; if the interval is greater than three years, it is recommended that two injections, 2-4 weeks apart, should be administered.
Boosters using FHV vaccines produced by another manufacturer are acceptable.
It is not known if cats that have recovered from acute disease caused by FHV might enjoy lifelong protection against new infections. Therefore, currently vaccination is still recommended even in cats that have been infected.
Disease control in specific situations
FHV infection is common in multi-cat households. Depending on the management, ABCD recommendations refer to either shelters or breeding catteries (see the ABCD guidelines “Infectious diseases in shelter situations and their management”).
FHV infections can pose a large problem in cat shelters. Management to prevent and limit the spread of infection is as important as vaccination. In shelters where incoming cats are mixed with resident ones, high infection rates are frequent. To control this situation, newcomers should be quarantined for three weeks, and kept individually – unless known to be from the same household. Shelter design and management measures should be aimed at avoiding cross infections. New cats should be vaccinated as soon as possible when they are healthy and no contraindications to vaccination have been found. If there is a particularly high risk, e.g. past or recent FHV infections, MLV vaccines are used, as these provide earlier protection. In an acute respiratory disease outbreak, identification of the agent involved – with differentiation between FHV and FCV – can be useful in deciding on the appropriate preventive measures.
Administration of a single dose of famciclovir (125 or 500 mg) in a shelter where 40% of cats were FHV positive had no effect on clinical score nor viral load in a placebo-controlled study (Litster et al., 2015) and is not recommended to prevent occurrence of acute clinical signs.
In a recent study, administration of famciclovir for 21 days to cats already presenting with URTD did reduce significantly the risk of worsening of clinical signs in the treated group compared to the placebo group; however, these preliminary results have to be confirmed in a larger study (Reinhard et al., 2020).
FHV infections can be a major problem in breeding catteries, where they most often appear in young kittens before weaning – typically between four to eight weeks of age, when MDA wanes. The source of infection is often the queen, who is the virus carrier and whose latent infection has been reactivated during kittening and lactation.
Infection in such young kittens is often severe, involving the entire litter. The level of mortality can be high, and some kittens that recover from acute disease are left with complications, notably chronic rhinitis. Vaccination of the queen to prevent infection of her kittens is not effective since vaccination does not prevent the development of FHV carrier status. However, if the queen has a good antibody titre, the kittens will benefit from the high levels of MDA transferred through the colostrum, which provide protection against disease during the first weeks of life.
Annual booster vaccinations of the queen might therefore be indicated, which should ideally take place prior to mating. Annual vaccination is not required once queens are no longer used for breeding purposes.
Queens should give birth in isolation, and litters should neither mix nor have contacts with other cats until they have been fully vaccinated. Early vaccination should be considered for litters from queens that had infected litters previously. The earliest age for which FHV vaccines are licensed is six weeks, but kittens can become susceptible to infection earlier than this when MDA wanes. Vaccination from four weeks of age can be considered in high-risk situations, to be repeated every two weeks until the primary vaccination course is given as usual.
Early weaning into isolation from four weeks of age is an alternative approach to protecting kittens from maternal infection, although behavioural problems can arise in kittens that have undergone early weaning and so this method is no longer recommended. There are no reliable tests that will identify latently infected queens and predict which can infect their kittens.
There is no evidence of FHV infecting humans.
ABCD Europe gratefully acknowledges the support of Boehringer Ingelheim (the founding sponsor of the ABCD), Virbac and IDEXX GmbH.
Belgard S, Truyen U, Thibault JC, Sauter-Louis C, Hartmann K (2010): Relevance of feline calicivirus, feline immunodeficiency virus, feline leukemia virus, feline herpesvirus and Bartonella henselae in cats with chronic gingivostomatitis. Berl Munch Tierarztl Wochenschr 123(9-10), 369-376.
Berger A, Willi B, Meli ML, Boretti FS, Hartnack S, Dreyfus A, Lutz H, Hofmann-Lehmann R (2015): Feline calicivirus and other respiratory pathogens in cats with Feline calicivirus-related symptoms and in clinically healthy cats in Switzerland. BMC Vet Res 11, 282.
Bergmann M, Ballin A, Schultz B, Dörfelt R, Hartmann K (2019): Treatment of acute viral feline upper respiratory tract infections. Tierarztl Prax Ausgabe K Kleintiere Heimtiere 47, 98-100.
Bergmann M, Speck S, Rieger A, Truyen U, Hartmann K, et al (2020): Antibody response to feline herpesvirus-1 vaccination in healthy adult cats. J Feline Med Surg 22(4), 329-338.
Binns SH, Dawson S, Speakman AJ, et al (2000): A study of feline upper respiratory tract disease with reference to prevalence and risk factors for infection with feline calicivirus and feline herpesvirus. J Feline Med Surg 2, 123-133.
Bol S, Bunnik EM (2015): Lysine supplementation is not effective for the prevention or treatment of feline herpesvirus 1 infection in cats: a systematic review. BMC Vet Res 11, 284.
Brooks SE, Kaza V, Nakamura T, Trousdale MD (1994): Photoinactivation of herpes simplex virus by rose bengal and fluorescein. In vitro and in vivo studies. Cornea 13, 43-50.
Burgener DC, Maes RK (1988): Glycoprotein-specific immune responses in cats after exposure to feline herpesvirus-1. Am J Vet Res 49, 1673-1676.
Burgesser KM, Hotaling S, Schiebel A, Ashbaugh SE, Roberts SM, Collins JK (1999): Comparison of PCR, virus isolation, and indirect fluorescent antibody staining in the detection of naturally occurring feline herpesvirus infections. J Vet Diagn Invest 11, 122-126.
Carmel LW, Lamberski N, Rideout BA, Vaida F, Citino SB, Barri MT, Haefele HJ, Junge RE, Murray S, Hungerford LL (2017): Epidemiology of clinical feline herpesvirus infection in zoo-housed cheetahs (Acinonyx jubatus). J Am Vet Med Assoc 251(8), 946–956.
Cave NJ, Dennis K, Gopakumar G, Dunowska M (2014): Effects of physiologic concentrations of l-lysine on in vitro replication of feline herpesvirus 1. Am J Vet Res 75, 572-580.
Contreras ET, Hodgkins E, Tynes V, Beck A, Olea-Popelka F, Lappin MR (2018): Effect of a Pheromone on Stress-Associated Reactivation of Feline Herpesvirus-1 in Experimentally Inoculated Kittens. J Vet Intern Med 32(1), 406-417.
Contreras ET, Olea-Popelka F, Wheat W, Dow S, Hawley J, Lappin MR (2019): Evaluation of liposome toll-like receptor ligand complexes for non-specific mucosal immunoprotection from feline herpesvirus-1 infection. J Vet Intern Med 33(2), 831-837.
Cooper AE, Thomasy SM, Drazenovich TL, Kass PH, Potnis SS, Leutenegger CM, Maggs DJ (2019): Prophylactic and therapeutic effects of twice-daily famciclovir administration on infectious upper respiratory disease in shelter-housed cats. J Feline Med Surg 21(6), 544-552.
Coutts AJ, Dawson S, Willoughby K, Gaskell RM (1994): Isolation of feline respiratory viruses from clinically healthy cats at UK cat shows. Vet Rec 135, 555-556.
Cullen CL, Wadowska DW, Singh A, Melekhovets Y (2005): Ultrastructural findings in feline corneal sequestra. Vet Ophthalmol 8, 295-303.
Czarnecki GL, Hirakawa DA, Baker DH (1985): Antagonism of arginine by excess dietary lysine in the growing dog. J Nutr 115(6), 743–752.
Dawson DA, Carman J, Collins J, Hill S, Lappin MR (1998): Enzyme-linked immunosorbent assay for detection of feline herpesvirus 1 IgG in serum, aqueous humour, and cerebrospinal fluid. J Vet Diagn Invest 10, 315-319.
Dawson S, Willoughby K, Gaskell RM, Woog G, Chalmers WCK (2001): A field trial to assess the effect of vaccination against feline herpesvirus, feline calicivirus and feline panleukopenia virus in 6-week-old kittens. J Feline Med Surg 3, 17-22.
De Lucia M, Cabre M, Denti D, Mezzalira G, Rondena M, Furlanello T (2021): Presumptive herpesvirus-associated erythema multiforme in a cat. Vet Dermatol 32(1), 86.
DiGangi BA, Levy JK, Griffin B, Reese MJ, Dingman PA, Tucker SJ, Dubovi EJ (2011): Effects of maternally-derived antibodies on serological responses to vaccination in kittens. J Feline Med Surg 14(2), 118-123.
Drazenovich TL, Fascetti AJ, Westermeyer HD, et al (2009): Effects of dietary lysine supplementation on upper respiratory and ocular disease and detection of infectious organisms in cats within an animal shelter. Am J Vet Res 70, 1391-1400.
Ellis TM (1981): Feline respiratory virus carriers in clinically healthy cats. Aust Vet J 57, 115-118.
Fernandez M, Manzanilla EG, Lloret A, León M, Thibault JC (2017): Prevalence of feline herpesvirus-1, feline calicivirus, Chlamydophila felis and Mycoplasma felis DNA and associated risk factors in cats in Spain with upper respiratory tract disease, conjunctivitis and/or gingivostomatitis. J Feline Med Surg 19(4), 461-469.
Fiorito F, Cantiello A, Granato GE, Navas L, Diffidenti C, De Martino L, Maharajan V, Olivieri F, Pagnini U, Iovane G (2016): Clinical improvement in feline herpesvirus 1 infected cats by oral low dose of interleukin-12 plus interferon-gamma. Comp Immunol Microbiol Infect Dis 48, 41-47.
Fontenelle JP, Powell CC, Veir JK, Radecki SV, Lappin MR (2008): Effect of topical ophthalmic application of cidofovir on experimentally induced primary ocular feline herpesvirus-1 infection in cats. Am J Vet Res 69, 289-293.
Gaskell RM (1974): Feline Viral Rhinotracheitis: The Carrier State. Thesis, University of Bristol.
Gaskell R, Dawson S, Radford A (2006): Feline respiratory disease. In: Greene CE, ed. Infectious diseases of the dog and cat. Missouri: WB Saunders, 145-154.
Gaskell R, Dawson S, Radford A, Thiry E (2007): Feline herpesvirus. Vet Res 38, 337-354.
Gaskell RM, Povey RC (1977): Experimental induction of feline viral rhinotracheitis (FVR) virus re-excretion in FVR-recovered cats. Vet Rec 100, 128-133.
Gaskell RM, Povey RC (1979): The dose response of cats to experimental infection with feline viral rhinotracheitis virus. J Comp Pathol 89, 179-191.
Gaskell RM, Povey RC (1982): Transmission of feline viral rhinotracheitis. Vet Rec 111, 359-362.
Gore TC, Lakshmanan N, Williams JR, Jirjis FF, Chester ST, Duncan KL, Coyne MJ, Lum MA, Sterner FJ (2006): Three-year duration of immunity in cats following vaccination against feline rhinotracheitis virus, feline calicivirus, and feline panleukopenia virus. Vet Ther 7(3), 213-222.
Gould D (2011): Feline herpesvirus-1. Ocular manifestations, diagnosis and treatment options. J Feline Med Surg 13, 333-346.
Haid C, Kaps S, Gönczi E, et al (2007): Pretreatment with feline interferon omega and the course of subsequent infection with feline herpesvirus in cats. Vet Ophthalmol 10, 278-284.
Hamano M, Maeda K, Mizukoshi F, Mochizuki M, Tohya Y, Akashi H, Kai K (2004): Genetic rearrangements in the gC gene of the feline herpesvirus type 1. Virus genes 28, 55-60.
Hara M, Fukuyama M, Suzuki Y, Kisikawa S, Ikeda T, Kiuchi A, Tabuchi K (1996): Detection of feline herpes virus 1 DNA by the nested polymerase chain reaction. Vet Microbiol 48, 345-352.
Hargis AM, Ginn PE (1999): Ulcerative facial and nasal dermatitis and stomatitis in cats associated with feline herpesvirus-1. Vet Dermatol 10, 267-274.
Hartley C (2010): Aetiology of corneal ulcers. Assume FHV-1 unless proven otherwise. J Feline Med Surg 12, 24-35.
Helps CR, Lait P, Damhuis A, et al (2005): Factors associated with upper respiratory tract disease caused by feline herpesvirus, feline calicivirus, Chlamydophila felis and Bordetella bronchiseptica in cats: experience from 218 European catteries. Vet Rec 159, 669-673.
Helps C, Reeves N, Egan K, Howard P, Harbour D (2003): Detection of Chlamydophila felis and feline herpesvirus by multiplex real-time PCR analysis. J Clin Microbiol 41, 2734-2736.
Henderson SM, Bradley K, Day MJ, et al (2004): Investigation of nasal disease in the cat – a retrospective study of 77 cases. J Feline Med Surg 6, 245-257.
Hoover EA, Griesemer RA. (1971): Experimental feline herpesvirus infection in the pregnant cat. Am J Pathol. Oct;65(1):173-88.
Holland JL, Outerbridge CA, Affolter VK, Maggs DJ. (2006): Detection of feline herpesvirus 1 DNA in skin biopsy specimens from cats with or without dermatitis. J Am Vet Med Assoc. Nov 1;229(9):1442-6.
Jas D, Aeberle C, Lacombe V, Guiot AL, Poulet H (2009): Onset of immunity in kittens after vaccination with a non-adjuvanted vaccine against feline panleucopenia, feline calicivirus and feline herpesvirus. Vet J 182, 86–93.
Jas D, Frances-Duvert V, Vernes D, Guigal PM, Poulet H (2015): Three-year duration of immunity for feline herpesvirus and calicivirus evaluated in a controlled vaccination-challenge laboratory trial. Vet Microbiol 177(1-2), 123-131.
Johnson LR, Foley JE, De Cockc HE, Clarke HE, Maggs DJ (2005): Assessment of infectious organisms associated with chronic rhinosinusitis in cats. J Am Vet Med Assoc 227, 579-585.
Johnson RP, Povey RC (1985): Vaccination against feline viral rhinotracheitis in kittens with maternally derived feline viral rhinotracheitis antibodies. J Am Vet Med Assoc 186,149-152.
Jongh O (2004): A cat with herpetic keratitis (primary stage of infection) treated with feline omega interferon. In: Karine de Mari (ed.): Veterinary Interferon Handbook. Carros: Virbac, 138-147.
Kuroda Y, Yamagata H, Nemoto M, Inagaki K, Tamura T, Maeda K (2019): Antiviral effect of sinefungin on in vitro growth of feline herpesvirus type 1. J Antibiot (Tokyo) 72(12), 981-985.
Lamb CR, Richbell S, Mantis P (2003): Radiographic signs in cats with nasal disease. J Feline Med Surg 5, 227-235.
Lappin MR, Andrews J, Simpson D, Jensen WA (2002): Use of serologic tests to predict resistance to feline herpesvirus 1, feline calicivirus, and feline parvovirus infection in cats. J Am Vet Med Assoc 220, 38-42.
Lappin MR, Sebring RW, Porter M, Radecki SJ, Veir J (2006): Effects of a single dose of an intranasal feline herpesvirus 1, calicivirus, and panleukopenia vaccine on clinical signs and virus shedding after challenge with virulent feline herpesvirus 1. J Feline Med Surg 8, 158-163.
Lappin MR, Veir J, Hawley J (2009): Feline panleukopenia virus, feline herpesvirus-1, and feline calicivirus antibody responses in seronegative specific pathogen-free cats after a single administration of two different modified live FVRCP vaccines. J Feline Med Surg 11, 159-162.
Lappin MR, Vei JK, Satyaraj E, Czarnecki-Maulden G (2009b): Pilot study to evaluate the effect of oral supplementation of Enterococcus faecium SF68 on cats with latent feline herpesvirus 1. J Feline Med Surg 11, 650-654.
Lappin MR (2012): Feline panleukopenia virus, feline herpesvirus-1 and feline calicivirus antibody responses in seronegative specific pathogen-free kittens after parenteral administration of an inactivated FVRCP vaccine or a modified live FVRCP vaccine. J Feline Med Surg 14(2), 161-164.
Lappin MR, Blondeau J, Boothe D, Breitschwerdt EB, Guardabassi L, Lloyd DH, Papich MG, Rankin SC, Sykes JE, Turnidge J, Weese JS (2017): Antimicrobial use Guidelines for Treatment of Respiratory Tract Disease in Dogs and Cats: Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases. J Vet Intern Med 31(2), 279-294.
Legendre AM, Kuritz T, Heidel RE, Baylor VM (2017): Polyprenyl Immunostimulant in Feline Rhinotracheitis: Randomized Placebo-Controlled Experimental and Field Safety Studies. Front Vet Sci 4,24.
Lewin AC, Coghill LM, McLellan GJ, Bentley E, Kousoulas KG (2020): Genomic analysis for virulence determinants in feline herpesvirus type-1 isolates. Virus Genes 56(1), 49-57.
Lewin AC, Liu CC, Alling C, Camacho-Luna P, Miessler B, Carter RT (2020b): In vitro efficacy of ganciclovir against feline herpesvirus type 1 and assessment of ocular tolerability in healthy cats. J Feline Med Surg 4,1098612X20944363.
Litster AL, Lohr BR, Bukowy RA, Thomasy SM, Maggs DJ (2015): Clinical and antiviral effect of a single oral dose of famciclovir administered to cats at intake to a shelter. Vet J 203(2), 199-204.
Litster A, Wu CC, Leutenegger CM (2015a): Detection of feline upper respiratory tract disease pathogens using a commercially available real-time PCR test. Vet J 206(2), 149-153.
Liu MZ, Han XH, Yao LQ, Zhang WK, Liu BS, Chen ZL (2019): Development and application of a simple recombinase polymerase amplification assay for rapid point-of-care detection of feline herpesvirus type 1. Arch Virol 164(1), 195-200.
Maggs DJ (2001): Update on the diagnosis and management of feline herpesvirus-1 infection. In: August JR (ed.): Consultations in Feline Internal Medicine Volume 4, Philadelphia: WB Saunders Company: 51-61.
Maggs DJ (2005): Update on pathogenesis, diagnosis, and treatment of feline herpesvirus type 1. Clin Tech Small Anim Pract 20, 94-101.
Maggs DJ (2010): Antiviral therapy for feline herpesvirus infections. Vet Clin North Am Small Anim Pract 40, 1055-1062.
Maggs DJ, Clarke HE (2004): In vitro efficacy of ganciclovir, cidofovir, penciclovir, foscarnet, idoxuridine, and acyclovir against feline herpesvirus type-1. Am J Vet Res 65, 399-403.
Maggs DJ, Clarke HE (2005): Relative sensitivity of polymerase chain reaction assays used for detection of feline herpesvirus type 1 DNA in clinical samples and commercial vaccines. Am J Vet Res 66, 1550-1555.
Maggs DJ, Lappin MR, Nasisse MP (1999a): Detection of feline herpesvirus-specific antibodies and DNA in aqueous humor from cats with and without uveitis. Am J Vet Res 60, 932-936.
Maggs DJ, Lappin MR, Reif JS, et al (1999b): Evaluation of serologic and viral detection methods for diagnosing feline herpesvirus-1 infection in cats with acute respiratory tract or chronic ocular disease. J Am Vet Med Assoc 214, 502-507.
Maggs DJ, Nasisse MP, Kass PH (2003): Efficacy of oral supplementation with L-lysine in cats latently infected with feline herpesvirus. Am J Vet Res 64, 37-42.
Maggs DJ, Sykes JE, Clarke HE, et al (2007): Effects of dietary lysine supplementation in cats with enzootic upper respiratory disease. J Feline Med Surg 9, 97-108.
Malik R, Lessels NS Meek M, et al (2009): Treatment of feline herpesvirus-1 associated disease in cats with famciclovir and related drugs. J Feline Med Surg 11, 40-48.
Marsilio F, Di Martino B, Aguzzi I, Meridiani I (2004): Duplex polymerase chain reaction assay to screen for feline herpesvirus-1 and Chlamydophila spp. in mucosal swabs from cats. Vet Res Commun 28, 295-298.
Monne Rodriguez J, Köhler K, Kipar A (2018): Calicivirus co-infections in herpesvirus pneumonia in kittens. Vet J 236, 1-3.
Mouzin DE, Lorenzen MJ, Haworth JD, King VL (2004): Duration of serologic response to three viral antigens in cats. J Am Vet Med Assoc 224, 61-66.
Munks MW, Montoya AM, Pywell CM, Talmage G, Forssen A, Campbell TL, Dodge DD, Kappler JW, Marrack P (2017): The domestic cat antibody response to feline herpesvirus-1 increases with age. Vet Immunol Immunopathol 188, 65-70.
Nakanishi H, Furuya M, Soma T, Hayashiuchi Y, Yoshiuchi R, Matsubayashi M, Tani H, Sasai K (2019): Prevalence of microorganisms associated with feline gingivostomatitis. J Feline Med Surg 21(2), 103-108.
Nasisse MP, Glover TL, Moore CP, Weigler BJ (1998): Detection of feline herpesvirus 1 DNA in corneas of cats with eosinophilic keratitis or corneal sequestration. Am J Vet Res 59, 856-858.
Nasisse MP, Guy JS, Davidson MG, Sussman WA, Fairley NM (1989): Experimental ocular herpesvirus infection in the cat. Sites of virus replication, clinical features and effects of corticosteroid administration. Invest Ophthalmol Vis Sci 30, 1758-1768.
Nasisse MP, Guy JS, Stevens JB, English RV, Davidson MG (1993): Clinical and laboratory findings in chronic conjunctivitis in cats: 91 cases (1983-1991). J Am Vet Med Assoc 203, 834-837.
Nasisse MP, Weigler BJ (1997): The diagnosis of ocular herpes virus infection. Vet Comp Ophthalmol 7, 44-51.
Nemanic S, Hollars K, Nelson NC, Bobe G (2015): Combination of computed tomographic imaging characteristics of medial retropharyngeal lymph nodes and nasal passages aids discrimination between rhinitis and neoplasia in cats. Vet Radiol Ultrasound 56(6), 617-627. doi: 10.1111/vru.12279. Epub 2015 Jul 20
Pedersen NC (1987): Feline herpesvirus type 1 (feline rhinotracheitis virus). In: Appel MJ (ed.): Virus infections of carnivores. Amsterdam: Elsevier science publishers: 227-237.
Pedersen NC, Satop R, Foley JE, Poland AM (2004): Common virus infections in cats, before and after being placed in shelters, with emphasis on Feline enteric coronavirus. J Feline Med Surg 6, 83-88.
Pennington MR, Fort MW, Ledbetter EC, Van de Walle GR (2016): A novel corneal explant model system to evaluate antiviral drugs against feline herpesvirus type 1 (FHV-1). J Gen Virol 97(6),1414-1425.
Poulet H (2007): Alternative early life vaccination programs for companion animals. J Comp Path 137, S67-S71.
Povey RC, Johnson RH (1970): Observations on the epidemiology and control of viral respiratory disease in cats. J Small Anim Pract 11, 485-494.
Reagan KL, Hawley JR, Lappin MR (2014): Concurrent administration of an intranasal vaccine containing feline herpesvirus-1 (FHV-1) with a parenteral vaccine containing FHV-1 is superior to parenteral vaccination alone in acute FHV-1 challenge model. Vet J 201, 202-206.
Reed N, Gunn-Moore D (2012): Nasopharyngeal disease in cats. 1. Diagnostic investigation. J Feline Med Surg 14, 306-315.
Rees TM, Lubinski JL (2008): Oral supplementation with L-lysine did not prevent upper respiratory infection in a shelter population of cats. J Feline Med Surg 10, 510-513.
Reinhard CL, McCobb E, Stefanovski D, Sharp CR (2020): A Randomized, Placebo-Controlled Clinical Trial of Famciclovir in Shelter Cats with Naturally Occurring Upper Respiratory Tract Disease. Animals (Basel) 10(9), 1448.
Reubel GH, Ramos RA, Hickman MA, Rimstad E, Hoffmann DE, Pedersen NC (1993): Detection of active and latent infections using the polymerase chain reaction. Arch Virol 132, 409-420.
Schoenborn WC, Wisner ER, Kass PP, Dale M (2003): Retrospective assessment of computed tomographic imaging of feline sinonasal disease in 62 cats. Vet Radiol Ultrasound 44, 185-195.
Schulz C, Hartmann K, Mueller RS, Helps C, Schulz BS (2015): Sampling sites for detection of feline herpesvirus-1, feline calicivirus and Chlamydia felis in cats with feline upper respiratory tract disease. J Feline Med Surg 17(12), 1012-1019.
Scott FW, Geissinger CM (1999): Long-term immunity in cats vaccinated with an inactivated trivalent vaccine. Am J Vet Res 60, 652–658.
Sebbag L, Sara M, Leland A, Mukai M, Soohyun K, Maggs DJ (2021): Altered Corneal Innervation and Ocular Surface Homeostasis in FHV-1-Exposed Cats: A Preliminary Study Suggesting Metaherpetic Disease. Front Vet Sci 7, 580414.
Segarra S, Papasouliotis K, Helps C (2011): The in vitro effects of proxymetacaine, fluorescein, and fusidic acid on real-time PCR assays used for the diagnosis of Feline herpesvirus 1 and Chlamydophila felis infections. Vet Ophthalmol 14, Suppl 15-8.
Slater Y, York C (1976): Comparative studies on parenteral and intranasal inoculation of an attenuated feline herpes virus. Dev Biol Stand 33, 410-416.
Spatz SJ, Rota PA, Maes RK (1994): Identification of the feline herpesvirus type 1 (FHV-1) genes encoding glycoproteins G, D, I and E: expression of FHV-1 glycoprotein D in vaccinia and raccoon poxviruses. J Gen Virol 75, 1235-1244.
Spertus CB, Pennington MR, Van de Walle GR, Badanes ZI, Judd BE, Mohammed HO, Ledbetter EC (2019): Effects of orally administered raltegravir in cats with experimentally induced ocular and respiratory feline herpesvirus-1 infection. Am J Vet Res 80(5), 490-497.
Stiles J, McDermott M, Bigsby D, et al (1997a): Use of nested polymerase chain reaction to identify feline herpesvirus in ocular tissue from clinically normal cats and cats with corneal sequestra or conjunctivitis. Am J Vet Res 58, 338-342.
Stiles J, McDermott M, Willis M, Roberts W, Green C (1997b): Comparison of nested polymerase chain reaction, virus isolation, and fluorescent antibody testing for identifying feline herpesvirus in cats with conjunctivitis. Am J Vet Res 58, 804-847.
Stiles J, Townsend WM, Rogers QR, Krohne SG (2002): Effect of oral administration of L-lysine on conjunctivitis caused by feline herpesvirus in cats. Am J Vet Res 63, 99–103.
Storey ES, Gerding PA, Scherba G, Schaeffer DJ (2002): Survival of equine herpesvirus-4, feline herpesvirus-1, and feline calicivirus in multidose ophthalmic solutions. Vet Ophthalmol 5, 263-267.
Summers SC, Ruch-Gallie R, Hawley JR, Lappin MR, Summers SC, et al. (2017): Effect of modified live or inactivated feline herpesvirus-1 parenteral vaccines on clinical and laboratory findings following viral challenge. J Feline Med Surg 19(8), 824-830.
Sykes JE, Allen JL, Studdert VP, Browning GF (2001): Detection of feline calicivirus, feline herpesvirus 1 and Chlamydia psittaci mucosal swabs by multiplex RT-PCR/PCR. Vet Microbiol 81, 95-108.
Tan Y, Dong G, Xu H, Niu J, Lu W, Wang K, Dong H, Zhang S, Huang H, Hu G (2020): Development of a cross-priming isothermal amplification assay based on the glycoprotein B gene for instant and rapid detection of feline herpesvirus type 1. Arch Virol 165(3), 743-747.
Thiry E (2006): Feline Herpesvirus. In Clinical virology of the dog and cat (Collection Clinical Virology). Éditions du Point Vétérinaire, Maisons-Alfort (France): 91-97.
Thiry E, Addie D, Belák S, Boucraut-Baralon C, Egberink H, Frymus T, Gruffydd-Jones T, Hartmann K, Hosie MJ, Lloret A, Lutz H, Marsilio F, Pennisi MG, Radford AD, Truyen U, Horzinek MC (2009): Feline herpesvirus infection. ABCD guidelines on prevention and management. J Feline Med Surg 11(7), 547-555.
Thomasy SM, Lim CC, Reilly CM, Kass PH, Lappin MR, Maggs DG (2011): Evaluation of orally administered famciclovir in cats experimentally infected with feline herpesvirus type-1. Am J Vet Res 72, 85-95.
Thomasy SM, Maggs DJ (2016): A review of antiviral drugs and other compounds with activity against feline herpesvirus type 1. Vet Ophthalmol 19 (Suppl 1), 119-130.
Thomasy SM, Shull O, Outerbridge CA, Lim CC, Freeman KS, Strom AR, Kass PH, Maggs DJ (2016): Oral administration of famciclovir for treatment of spontaneous ocular, respiratory, or dermatologic disease attributed to feline herpesvirus type 1: 59 cases (2006-2013). J Am Vet Med Assoc 249(5), 526-538.
Townsend WM, Jacobi S, Tai S, Kiupel M, Wise AG, Maes RK (2013): Ocular and neural distribution of feline herpesvirus-1 during active and latent experimental infection in cats. BMC Vet Res 9, 185.
Tronblee C, Jones JC, Etue AE, Forrester SD (2006): Association between clinical characteristics, computed tomography characteristics, and histologic diagnosis for cats with sinonasal disease. Vet Radiol Ultrasound 47, 241-248.
Troyer RM, Beatty JA, Stutzman-Rodriguez KR, Carver S et al (2014): Novel gammaherpesviruses in North American domestic cats, bobcats and pumas: identification, prevalence and risk factors. J Virol 10.1128/JVI.03405-13.
Van der Meulen K, Garre B, Croubels S, Nauwynck H (2006): In vitro comparison of antiviral drugs against feline herpesvirus 1. BMC Vet Res 26, 13.
Villatoro AJ, Claros S, Fernández V, Alcoholado C, Fariñas F, Moreno A, Becerra J, Andrades JA (2018): Safety and efficacy of the mesenchymal stem cell in feline eosinophilic keratitis treatment. BMC Vet Res 14(1), 116.
Vögtlin A, Fraefel C, Albini S, et al (2002): Quantification of feline herpesvirus 1 DNA in ocular fluid samples of clinically diseased cats by real-time TaqMan PCR. J Clin Microbiol 40, 519-523.
Wardley RC, Rouse BT, Babiuk LA (1976): Observations on recovery mechanisms from feline viral rhinotracheitis. Can J Comp Med 40, 257-264.
Weigler BJ, Babineau A, Sherry B, Nasisse MP (1997a): High sensitivity polymerase chain reaction assay for active and latent feline herpesvirus-1 infections in domestic cats. Vet Rec 140, 335-338.
Weigler BJ, Guy JS, Nasisse MP, Hancock SI, Sherry B (1997b): Effect of a live attenuated intranasal vaccine on latency and shedding of feline herpesvirus 1 in domestic cats. Arch Virol 142, 2389-2400.
Weiss RC (1989): Synergistic antiviral activities of acyclovir and recombinant human leukocyte (alpha) interferon on feline herpesvirus replication. Am J Vet Res 50, 1672-1677.
Westermeyer HD, Thomasy SM, Kado-Fong H, Maggs DJ (2009): Assessment of viremia associated with experimental primary feline herpesvirus infection or presumed herpetic recrudescence in cats. Am J Vet Res 70, 99-104.
Williams DL, Fitzmaurice T, Lay L, Forster K, Hefford J, Budge C, Blackmore K, Robinson JC, Field HF (2004): Efficacy of antiviral agents in feline herpetic keratitis: results of an in vitro study. Curr Eye Res 29, 215-218.
Williams DL, Robinson JC, Lay E, Field H (2005): Efficacy of topical aciclovir for the treatment of feline herpetic keratitis: results of a prospective clinical trial and data from in vitro investigations. Vet Rec 157, 254-257.
Witte CL, Lamberski N, Rideout BA, Vaida F, Citino SB, Barrie MT, Haefele HJ, Junge RE, Murray S, Hungerford LL (2017): Epidemiology of clinical feline herpesvirus infection in zoo-housed cheetahs (Acinonyx jubatus). J Am Vet Med Assoc 251(8), 946-956.
Zapirain Gastón J, Stengel C, Harbour D, Krieger S, Stampf S, Hartmann K (2004): Prävalenzen des felinen Herpesvirus-1, felinen Calicivirus und Chlamydophila felis in Mehrkatzenhaushalten. Kleintierprax 49, 689-698.
Zirofsky D, Rekers W, Powell C, Hawley J, Veir J, Lappin M (2018): Feline Herpesvirus 1 and Mycoplasma spp. Conventional PCR Assay Results From Conjunctival Samples From Cats in Shelters With Suspected Acute Ocular Infections. Top Companion Anim Med 33(2), 45-48.