The Feline Herpesvirus: An Overview
Maigan Espinili Maruquin
The feline herpesvirus infection is common and recurring ocular disease is common (Stiles 2000). It is the most studied infectious cause of ocular surface disease in cats (Andrew 2001). Developing latent infections may recrudesce at later points in life of an infected cat (Stiles 2000).
I. Structure and Replication
Fig. 01. Structure of Herpes Virus. https://www.slideteam.net/0814-herpes-virus-medical-images-for-powerpoint.html
The feline herpesvirus (FHV 1) causes feline viral rhinotracheitis (FVR) (Gaskell and Wardley 1978, Gaskell, Dawson et al. 2007, Henzel, Brum et al. 2012). This virus is double-stranded DNA with a glycoprotein-lipid envelope and is a member of the Varicellovirus genus in the Alphaherpesvirinae subfamily (Gaskell, Dawson et al. 2007). This virus was also found out to be relatively fragile in the external environment and is highly susceptible to the effects of common disinfectants (Scott 1980, Eleraky, Potgieter et al. 2002, Gaskell, Dawson et al. 2007).
The FHV- 1 has short replication cycle, rapid cell-to-cell spread, has tendency to induce cell lysis, and displays persistence in sensory ganglia of their host (Gould 2011). It replicates in epithelial cells of both the conjunctiva and upper respiratory tract, and in neurons. The neuronal infection can lead to a lifelong latency after the primary infection (Thiry, Addie et al. 2009). For 18 hours, it can survive in damp environment, less in dry conditions and is also recorded to be relatively unstable as an aerosol (Povey and Johnson 1970, Donaldson and Ferris 1976, Stiles 2000, Gaskell, Dawson et al. 2007, Gould 2011).
II. Infection and Epidemiology
There are only three main genotype groups recognized for FHV-1 strains with very little genomic variations (Gould 2011). The virus sheds in ocular, nasal, and oral secretions with large transmission by direct contact with an infected cat. Although one of the most important sources of virus are the acutely infected cats, susceptible cats may also be infected by latently infected carrier cats (Gaskell and Povey 1982, Gaskell, Dawson et al. 2007). On the other hand, the environment may not be a primary source of transmission but catteries may cause indirect transmission through contaminated housing, feeding and cleaning utensils, and personnel (Gaskell, Dawson et al. 2007, Thiry, Addie et al. 2009).
Latently infected cats may also transmit FHV to their kittens due to the parturition and lactation inducing stress that may lead to viral reactivation and shedding, making kittens susceptible to the virus, depending on the level of maternally derived antibodies (MDA) they possess. High levels of MDA protects kittens against the disease and may develop subclinical infection leading to latency while insufficient MDA may lead to clinical signs (Gaskell and Povey 1982, Thiry, Addie et al. 2009).
Recovered cats become latently infected carriers and reactivation happens particularly after periods of stress (Gaskell, Dawson et al. 2007). However, it doesn’t shed immediately after the stress. It undergoes lag phase of 4–11 days, precedes the shedding from 1–13 days (Gaskell and Povey 1973, Gaskell and Povey 1977, Gaskell, Dawson et al. 2007). Further, risk factors associated with FeHV-1 shedding includes contact with other cats, the presence of upper respiratory disease, younger cats, poor hygiene, and larger households (Sykes, Anderson et al. 1999, Binns, Dawson et al. 2000, Helps, Lait et al. 2005, Gaskell, Dawson et al. 2007).
Infection routes include nasal, oral, and conjunctival mucous membranes and is primarily shed in secretions for 1–3 weeks following infection (Andrew 2001, Gaskell, Dawson et al. 2007). In pregnant queens, vaginitis was caused by intravaginal instillation virus and causes congenitally infected kittens while intravenous inoculation leads to transplacental infection and abortion (Bittle and Peckham 1971, Hoover and Griesemer 1971, Gaskell, Dawson et al. 2007).
After 1 to 2 exposure of naive animals to FHV-1, the viral replication happens and epithelial cell necrosis occur in the nasal turbinates, nasopharynx and conjunctival mucosa (Gaskell & Dawson 1998). Lytic infection of the nasal epithelium with spread to the conjunctivas, pharynx, trachea, bronchi and bronchioles occurs and lesions characterized by multifocal epithelial necrosis with neutrophil infiltration and inflammation are also observed. Moreover, neonates or hypothermic kittens display transient viraemia associated with mononuclear cells (Gaskell, Dawson et al. 2007, Thiry, Addie et al. 2009).
It has been recorded that almost all infected cats become lifelong carriers. During the latency period, virus was spread along the sensory nerves and neurons with viral genome doesn’t replicate. Whereas, reactivating stressors include lactation and moving into a new environment (Gaskell and Povey 1977, Gaskell and Povey 1982, Pedersen, Sato et al. 2004, Thiry, Addie et al. 2009). Lesions may be developed upon viral reactivation in adult cats and ‘recrudescence’ disease may also be a consequence (Thiry, Addie et al. 2009).
As high as 70% mortality rates was reported for infected kittens (Povey 1990). Although MDA may persist for 2 to 10 weeks, this may not protect cats from subclinical infection (Gaskell & Dawson 1998)(Andrew 2001).
IV. Clinical Signs
Generally, FHV- infected cats display acute upper respiratory and ocular disease with usually 2 to 6 days incubation period, or may be longer (Gaskell and Povey 1979, Stiles 2000, Gaskell, Dawson et al. 2007) with depression, fever, lethargy, inappetence, pyrexia, sneezing, coughing, nasal discharge, and conjunctivitis with ocular discharge depending on the viral exposure and individual susceptibility (Hoover, Rohovsky et al. 1970, Crandell 1973, Stiles 2000, Gaskell, Dawson et al. 2007, Thiry, Addie et al. 2009) (Gaskell R.M., Dawson S, 1994). Also, excessive salivation with drooling may also be observed during the initial clinical signs of the disease (Gaskell, Dawson et al. 2007).Once the virus reaches the lungs, pneumonia may kill the infected kittens (Stiles 2000, Thiry, Addie et al. 2009) (Gaskell R, et al. 2006).
The primary FHV- 1 infection with secondary bacterial infection leads in conjunctivitis sometimes with severe hyperemia and chemosis. The conjunctivitis is manifested as hyperaemia or redness with serous discharge, progressing to mucopurulent ocular discharge whereas, chemosis is swelling or oedema of the conjunctiva which may occur to a lesser extent (Stiles 2000, Andrew 2001, Gaskell, Dawson et al. 2007, Gould 2011).
In some cases, oral and skin ulcers, dermatitis, neurological signs and stomatitis syndrome occurs, characterized by eosinophilic infiltration, which is occasionally persistent (Hargis and Ginn 1999, Gaskell, Dawson et al. 2007, Thiry, Addie et al. 2009) (Gaskell R, et al. 2006) (Hargis AM, Ginn PE, 1999). Abortion is less frequent as compared to other herpesviruses and is most likely an indirect effect of the virus, instead due to the severe systemic effects of the illness (Hoover and Griesemer 1971, Gaskell, Dawson et al. 2007, Thiry, Addie et al. 2009).
Acute primary infection of FHV- 1 in the corneal epithelial cell results to corneal ulceration (Gould 2011) which is associated with the spread of the virus to the corneal epithelium (Stiles 2000). When these ulcers progresses, it leads to the involvement of deeper stromal layers (Stiles 2000) which is very significant due to its potential vision-threatening stromal opacification and scarring (Nasisse 1990, Andrew 2001). These corneal ulcers and severe conjunctivitis, with the occurrence of chemosis may lead to symblepharon involving the cornea (Stiles 2000). This may cause inability to blink, destruction of the lacrimal gland ductules (with resultant functional keratoconjunctivitis sicca [KCS]), and conjunctivalisation of the cornea, leading to blindness (Maggs 2005, Thiry, Addie et al. 2009, Gould 2011).
Secondary to chronic corneal ulceration may lead to the formation of corneal sequestra. It is the degeneration of a focal area of corneal stroma and is associated with a brown/black discolouration as the sequestrum progresses (Stiles 2000, Gould 2011).
Clinically, progressive form of corneal disease is an infiltrative, irregular, white/pink vascular in the conjunctiva and/or cornea in cats as a manifestation of eosinophilic conjunctivitis or keratitis (Andrew 2001, Gould 2011) (Glaze MB, Gelatt KN 1999).
Systemic immunosuppression, environmental stress (boarding, surgery, moving to a new environment, addition of a new pet) or systemic corticosteroid administration are considered to be factors for the reactivation of latent virus (Andrew 2001).
Acute phase on FHV- 1 infection is usually diagnosed on ocular and respiratory clinical signs alone, although sometimes laboratory testing is necessary (Stiles 2000, Andrew 2001). For conjunctivitis, fluorescent antibody testing is performed however, it has already been superseded by virus isolation (VI) and PCR testing (Gould 2011).
The virus isolation technique identifies live virus which is the diagnostic ‘gold standard’ for active infection. For the testing, swabs are collected from the conjunctival or corneal surface. The Polymerase Chain Reaction, on the other hand, has the ability to identify FHV-1 by amplifying specific sequences of viral DNA. (Gould 2011). With 100% specificity and extremely high sensitivity, various protocols has been developed (Hara, Fukuyama et al. 1996, Stiles, McDermott et al. 1997, Helps, Reeves et al. 2003, Gould 2011).
VI. Disease Management and Vaccination
Fluids, electrolytes and acid–base balance should be restored from losses due to salivation and reduced food. Intravenous administration may be required. Appetite stimulants may be used to improve food intake (Thiry, Addie et al. 2009). Whereas, preventing prevent secondary bacterial infections is necessary using broad-spectrum systemic antibiotics (Stiles 2000, Thiry, Addie et al. 2009). Cleansing of the eyes and administration of eye drops, wiping of nasal discharge several times daily and using saline and a local ointment may be helpful (Stiles 2000, Thiry, Addie et al. 2009). Supportive care is important including prevention of secondary bacterial conjunctival infection (Andrew 2001).
Antiviral drugs have been proposed to treat FHV ocular infections, including bromovinyldeoxyuridine, cidofovir, famciclovir, HPMA (N- [2- hydroxy propyl] methacryla mide), penciclovir, ribavirin, valaciclovir, vidarabine, foscarnet and lactoferrin (Malik, Lessels et al. 2009, Thiry, Addie et al. 2009). In some cases, topical anti-inflammatory drugs may help in FHV-1-related ocular diseases however, it has the risk of exacerbating the disease, like with the use of corticosteroids (Stiles 2000, Gould 2011). For recrudescent keratitis or conjunctivitis, it is important to identify and reduce or manage any potential stressors and antiviral drugs are used (Gould 2011).
The FHV- 1 infection is common and can be fatal thus vaccination is deemed important and recommended (Thiry, Addie et al. 2009) with re-vaccination intervals depending on the risk of exposure (Gaskell, Dawson et al. 2007). Genetic modifications were done in attempts to improve FHV- 1 vaccines (Gaskell, Dawson et al. 2007). Despite treatment options, no one therapy is successful in every cat (Stiles 2000)
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