Margaret J Hosie

Feline Herpesvirus Infection: ABCD Guidelines on Prevention and Management:

Overview Feline viral rhinotracheitis, caused by feline herpesvirus (FHV), is an upper respiratory tract disease that is often associated with feline calicivirus and bacteria. In most cats, FHV remains latent after recovery, and they become lifelong virus carriers. Stress or corticosteroid treatment may lead to virus reactivation and shedding in oronasal and conjunctival secretions. Infection Sick cats shed FHV in oral, nasal and conjunctival secretions; shedding may last for 3 weeks. Infection requires direct contact with a shedding cat. Disease signs Feline herpesvirus infections cause acute rhinitis and conjunctivitis, usually accompanied by fever, depression and anorexia. Affected cats may also develop typical ulcerative, dendritic keratitis. Diagnosis Samples consist of conjunctival, corneal or oropharyngeal swabs, corneal scrapings or biopsies. It is not recommended that cats recently vaccinated with a modified-live virus vaccine are sampled. Positive PCR results should be interpreted with caution, as they may be produced by low-level shedding or viral latency. Disease management ‘Tender loving care’ from the owner, supportive therapy and good nursing are essential. Anorexic cats should be fed blended, highly palatable food - warmed up if required. Mucolytic drugs (eg, bromhexine) or nebulisation with saline may offer relief. Broad-spectrum antibiotics should be given to prevent secondary bacterial infections. Topical antiviral drugs may be used for the treatment of acute FHV ocular disease. The virus is labile and susceptible to most disinfectants, antiseptics and detergents.

Feline immunodeficiency. ABCD guidelines on prevention and management.

Overview Feline immunodeficiency virus (FIV) is a retrovirus closely related to human immunodeficiency virus. Most felids are susceptible to FIV, but humans are not. Feline immunodeficiency virus is endemic in domestic cat populations worldwide. The virus loses infectivity quickly outside the host and is susceptible to all disinfectants. Infection Feline immunodeficiency virus is transmitted via bites. The risk of transmission is low in households with socially well-adapted cats. Transmission from mother to kittens may occur, especially if the queen is undergoing an acute infection. Cats with FIV are persistently infected in spite of their ability to mount antibody and cell-mediated immune responses. Disease signs Infected cats generally remain free of clinical signs for several years, and some cats never develop disease, depending on the infecting isolate. Most clinical signs are the consequence of immunodeficiency and secondary infection. Typical manifestations are chronic gingivostomatitis, chronic rhinitis, lymphadenopathy, weight loss and immune-mediated glomerulonephritis. Diagnosis Positive in-practice ELISA results obtained in a low-prevalence or low-risk population should always be confirmed by a laboratory. Western blot is the ‘gold standard’ laboratory test for FIV serology. PCR-based assays vary in performance. Disease management Cats should never be euthanased solely on the basis of an FIV-positive test result. Cats infected with FIV may live as long as uninfected cats, with appropriate management. Asymptomatic FIV-infected cats should be neutered to avoid fighting and virus transmission. Infected cats should receive regular veterinary health checks. They can be housed in the same ward as other patients, but should be kept in individual cages.

Feline Infectious Peritonitis ABCD Guidelines on Prevention and Management

Overview Feline Coronavirus infection is ubiquitous in domestic cats, and is particularly common where conditions are crowded. While most FCoV-infected cats are healthy or display only a mild enteritis, some go on to develop feline infectious peritonitis, a disease that is especially common in young cats and multi-cat environments. Up to 12% of FCoV-infected cats may succumb to FIP, with stress predisposing to the development of disease. Disease signs The ‘wet’ or effusive form, characterised by polyserositis (abdominal and/or thoracic effusion) and vasculitis, and the ‘dry’ or non-effusive form (pyogranulomatous lesions in organs) reflect clinical extremes of a continuum. The clinical picture of FIP is highly variable, depending on the distribution of the vasculitis and pyogranulomatous lesions. Fever refractory to antibiotics, lethargy, anorexia and weight loss are common non-specific signs. Ascites is the most obvious manifestation of the effusive form. Diagnosis The aetiological diagnosis of FIP ante-mortem may be difficult, if not impossible. The background of the cat, its history, the clinical signs, laboratory changes, antibody titres and effusion analysis should all be used to help in decisionmaking about further diagnostic procedures. At the time of writing, there is no non-invasive confirmatory test available for cats without effusion. Disease management In most cases FIP is fatal. Supportive treatment is aimed at suppressing the inflammatory and detrimental immune response. However, there are no controlled studies to prove any beneficial effect of corticosteroids.

Feline Leukaemia: ABCD Guidelines on Prevention and Management

Overview Feline leukaemia virus (FeLV) is a retrovirus that may induce depression of the immune system, anaemia and/or lymphoma. Over the past 25 years, the prevalence of FeLV infection has decreased considerably, thanks both to reliable tests for the identification of viraemic carriers and to effective vaccines. Infection Transmission between cats occurs mainly through friendly contacts, but also through biting. In large groups of non-vaccinated cats, around 30–40% will develop persistent viraemia, 30–40% show transient viraemia and 20–30% seroconvert. Young kittens are especially susceptible to FeLV infection. Disease signs The most common signs of persistent FeLV viraemia are immune suppression, anaemia and lymphoma. Less common signs are immune-mediated disease, chronic enteritis, reproductive disorders and peripheral neuropathies. Most persistently viraemic cats die within 2–3 years. Diagnosis In low-prevalence areas there may be a risk of false-positive results; a doubtful positive test result in a healthy cat should therefore be confirmed, preferably by PCR for provirus. Asymptomatic FeLV-positive cats should be retested. Disease management Supportive therapy and good nursing care are required. Secondary infections should be treated promptly. Cats infected with FeLV should remain indoors. Vaccination against common pathogens should be maintained. Inactivated vaccines are recommended. The virus does not survive for long outside the host.

Serological responses of cats to feline immunodeficiency virus.

The proteins of feline immunodeficiency virus (FIV) were identified by sodium dodecylsulphate poly-acrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Purified [35S]methionine/ cysteine-Iabelled virus contained proteins of M r 120, 24, 17, and 10kD, of which the most prominent were p24 and p17, and minor components of 62, 54, 52, 41 and 32kD. Sera from FIV-infected cats precipitated two glycoproteins (gp) of M r 120kD (gp120) and 41kD (gp41) from lysates of [14C]glucosamine-labelled infected cells. Purified virus contained very little or no detectable glycoproteins. The serological response to individual viral proteins was followed in experimentally infected cats by immunoblotting. Since purified virus was a poor source of gp120, a method using FIV-infected cell lysates was developed. Cats produced antibodies to gp120, p55, p24 and p17. (The p55 was presumed to be a precursor of p24 and p17.) Following infection, antibodies developed first to p24 and subsequently to p17, p55 and gp120. Sera from cats infected with three separate isolates of FIV, two from the UK and one from the USA, had cross-reacting antibodies to all of these viral proteins. The criteria for identification of seropositive cats were defined. The minimum requirement for a positive immunoblot was antibody to gp120 or to at least three core proteins (p55, p24 and p17). Comparison of two commercial enzyme-linked immunosorbent assay (ELISA) kits and immunoblotting indicated that false-positive results occurred as a result of non-specific reactions in the ELISA systems.

Enhancement after feline immunodeficiency virus vaccination

Cats were vaccinated with one of the three preparations: purified feline immunodeficiency virus (FIV) incorporated into immune stimulating complexes (ISCOMs), recombinant FIV p24 ISCOMs, or a fixed, inactivated cell vaccine in quil A. Cats inoculated with the FIV ISCOMs or the recombinant p24 ISCOMs developed high titres of antibodies against the core protein p24 but had no detectable antibodies against the env protein gp120 or virus neutralising antibodies. In contrast, all of the cats inoculated with the fixed, inactivated cell vaccine developed anti-env antibodies and four of five had detectable levels of neutralising antibody. However, none of the vaccinated cats were protected from infection after intraperitoneal challenge with 20 infectious units of FIV. Indeed there appeared to be enhancement of infection after vaccination as the vaccinated cats become viraemic sooner than the unvaccinated controls, and 100% of the vaccinated cats became viraemic compared with 78% of the controls. The mechanism responsible for this enhancement remains unknown.

Feline panleukopenia. ABCD guidelines on prevention and management

Overview Feline panleukopenia virus (FPV) infects all felids as well as raccoons, mink and foxes. This pathogen may survive in the environment for several months and is highly resistant to some disinfectants. Infection Transmission occurs via the faecal-oral route. Indirect contact is the most common route of infection, and FPV may be carried by fomites (shoes, clothing), which means indoor cats are also at risk. Intrauterine virus transmission and infection of neonates can occur. Disease signs Cats of all ages may be affected by FPV, but kittens are most susceptible. Mortality rates are high - over 90% in kittens. Signs of disease include diarrhoea, lymphopenia and neutropenia, followed by thrombocytopenia and anaemia, immunosuppression (transient in adult cats), cerebellar ataxia (in kittens only) and abortion. Diagnosis Feline panleukopenia virus antigen is detected in faeces using commercially available test kits. Specialised laboratories carry out PCR testing on whole blood or faeces. Serological tests are not recommended, as they do not distinguish between infection and vaccination. Disease management Supportive therapy and good nursing significantly decrease mortality rates. In cases of enteritis, parenteral administration of a broad-spectrum antibiotic is recommended. Disinfectants containing sodium hypochlorite (bleach), peracetic acid, formaldehyde or sodium hydroxide are effective.

Productive infection of T-helper lymphocytes with feline immunodeficiency virus is accompanied by reduced expression of CD4.

An antigen-specific feline T-lymphocyte cell line (Q201) was generated and infected in vitro with the feline immunodeficiency virus (FIV). Syncytium formation and the release of the viral core protein p24 into culture fluid were accompanied by a reduction in expression of the CD4 surface antigen. The reduction in CD4 expression was transient, the resulting persistently infected population of cells expressing levels of CD4 comparable to those observed prior to infection. Persistently infected cells gradually lost expression of major histocompatibility antigen (MHC) class II while maintaining pre-infection levels of expression of CD4, MHC class I, CD18 or CD29.

Differential Utilization of CD134 as a Functional Receptor by Diverse Strains of Feline Immunodeficiency Virus

ABSTRACT The feline homologue of CD134 (fCD134) is the primary binding receptor for feline immunodeficiency virus (FIV), targeting the virus preferentially to activated CD4+ helper T cells. However, with disease progression, the cell tropism of FIV broadens such that B cells and monocytes/macrophages become significant reservoirs of proviral DNA, suggesting that receptor utilization may alter with disease progression. We examined the receptor utilization of diverse strains of FIV and found that all strains tested utilized CD134 as the primary receptor. Using chimeric feline × human CD134 receptors, the primary determinant of receptor function was mapped to the first cysteine-rich domain (CRD1) of fCD134. For the PPR and B2542 strains, the replacement of CDR1 of fCD134 (amino acids 1 to 64) with human CD134 (hCD134) alone was sufficient to confer nearly optimal receptor function. However, evidence of differential utilization of CD134 was revealed, since strains GL8, CPGammer (CPG41), TM2, 0827, and NCSU1 required determinants in the region spanning amino acids 65 to 85, indicating that these strains may require a more stringent interaction for infection to proceed.

Vaccination with Inactivated Virus but Not Viral DNA Reduces Virus Load following Challenge with a Heterologous and Virulent Isolate of Feline Immunodeficiency Virus

ABSTRACT It has been shown that cats can be protected against infection with the prototypic Petaluma strain of feline immunodeficiency virus (FIVPET) using vaccines based on either inactivated virus particles or replication-defective proviral DNA. However, the utility of such vaccines in the field is uncertain, given the absence of consistent protection against antigenically distinct strains and the concern that the Petaluma strain may be an unrepresentative, attenuated isolate. Since reduction of viral pathogenicity and dissemination may be useful outcomes of vaccination, even in the absence of complete protection, we tested whether either of these vaccine strategies ameliorates the early course of infection following challenge with heterologous and more virulent isolates. We now report that an inactivated virus vaccine, which generates high levels of virus neutralizing antibodies, confers reduced virus loads following challenge with two heterologous isolates, FIVAM6 and FIVGL8. This vaccine also prevented the marked early decline in CD4/CD8 ratio seen in FIVGL8-infected cats. In contrast, DNA vaccines based on either FIVPET or FIVGL8, which induce cell-mediated responses but no detectable antiviral antibodies, protected a fraction of cats against infection with FIVPET but had no measurable effect on virus load when the infecting virus was FIVGL8. These results indicate that the more virulent FIVGL8 is intrinsically more resistant to vaccinal immunity than the FIVPET strain and that a broad spectrum of responses which includes virus neutralizing antibodies is a desirable goal for lentivirus vaccine development.