Feline immunodeficiency virus: where are we now? · Feline immunodeficiency virus (FIV) is a...

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Page 26 - VETcpd - Vol 2 - Issue 3 Peer Reviewed Feline immunodeficiency virus: where are we now? Feline immunodeficiency virus (FIV) is a lentivirus that is most commonly transmitted between cats by biting. Many different strains of the virus exist and different mutations can occur even within one infected individual. FIV-infected cats can live symptom-free for years but, due to the virus attacking CD4 lymphocytes, there is a progressive decline in immunity; with some cats eventually developing Feline Acquired Immunodeficiency Syndrome. Clinical signs of FIV infection are often associated with secondary infections due to immunosuppression. However, primary effects of FIV include inflammatory ocular diseases, renal disease and haematology abnormalities. There is no effective treatment for FIV that improves life expectancy, but there are treatment options that may improve clinical signs, along with treatment of secondary infections. There is a vaccine available for FIV in USA, Australia and New Zealand. Many cats with FIV can live long and happy lives if they are managed correctly and receive appropriate healthcare. Key words: feline immunodeficiency virus, immunodeficiency, retrovirus, antiviral treatment, immunomodulatory therapy Introduction Feline immu- nodeficiency virus (FIV) was first described in 1987, in a colony of rescue cats in California, USA, who were showing clinical signs of immune-deficiency (Pedersen et al. 1987). The clinical signs of FIV infection vary greatly between individual cats yet the disease was the most com- monly reported cause of mortality in adoption centres in the United Kingdom (UK) in one study (Murray at al. 2008). Today FIV remains a source of fear and misunderstanding amongst both owners and veterinary professionals with many FIV-infected cats euthanased at diagnosis. Recent studies demonstrating comparable lifespans between infected and uninfected cats add evidence to opinion that a posi- tive FIV blood test does not need to be an immediate death sentence for a cat and many FIV positive cats can live for several healthy years after diagnosis. Understand- ing how to diagnose FIV and knowing the clinical signs and possible treatments can all help with informed decision mak- ing regarding this disease. What is FIV? FIV is a retrovirus, part of the Genus called Lentiviruses, named after ‘Lentus’ which is Latin for slow (Figure 1) and is closely related to human immunodeficiency virus VET cpd - Feline: FIV Update Helen Bolter BVSc MRCVS Helen graduated from Bristol Veterinary School in 2008 and, in the same year, received an award from Cats’ Protection for a research proposal into blood pressure monitoring in geriatric cats. Having worked in small animal practice for just under a year, Helen went to South Africa and Namibia to work with big cats. Helen currently runs cat-only clinics in the UK. She has an interest in geriatric medicine, having herself re-homed several feline old age pensioners. Helen is also a tutor on International Cat Care’s Cat Professional and Feline Nursing distance education courses. (HIV). These complex retroviruses contain the important genes gag, pol and env, encoding for capsid protein p24 (impor- tant for diagnosis), reverse transcriptase enzymes (important for the virulence of the virus), and viral proteins (determining viral diversity) respectively. FIV has a high mutation rate because the reverse tran- scriptase enzyme is often inaccurate and creates genetic errors. This leads to the circulation of many heterologous strains, even within a single infected cat. Some of these mutations may lead to changes in virulence, and so the prognosis for each infected cat can vary a great deal. FIV is found world-wide. There are five distinct variants of the virus, known as clades or subtypes, found in different geographical areas and with significant diversity in the env gene. These five subtypes have been identified based on nucleotide sequence differences or the coding for the viral envelope or poly- merase. Also, within each clade there are genetic variations; some isolates being more pathogenic than others. The five clades are named A through E, with A being the only clade found in the UK and with B being the most common, found in other parts of the world, including Japan and the USA. Interestingly FIV is also found in wild big cat populations, includ- ing lions and puma, with endemic, high prevalence infections reported, and clades different from those affecting domestic cats (Carpenter et al. 1996, Brown et al. 1994). For Feline Referrals in your area: vetindex.co.uk/feline For Lab Tests and Equipment: vetindex.co.uk/Lab ® 16th Edition 15 THE A-Z DIRECTORY OF VETERINARY PRODUCTS, SUPPLIES AND SERVICES THE A-Z DIRECTORY OF VETERINARY PRODUCTS, SUPPLIES AND SERVICES 2015 www.vetindex.co.uk 21st Edition Vet CPD Journal: Includes 5 hours of FREE CPD! See inside for further details!!! Vet CPD VETcpd Vet CPD Journal VETcpd Vet CPD Journal VETcpd Vet CPD Journal VETcpd 5 hours FREE CPD!!

Transcript of Feline immunodeficiency virus: where are we now? · Feline immunodeficiency virus (FIV) is a...

Page 1: Feline immunodeficiency virus: where are we now? · Feline immunodeficiency virus (FIV) is a lentivirus that is most commonly transmitted between cats by biting. Many different strains

Page 26 - VETcpd - Vol 2 - Issue 3

Peer Reviewed

Feline immunodeficiency virus: where are we now?Feline immunodeficiency virus (FIV) is a lentivirus that is most commonly transmitted between cats by biting. Many different strains of the virus exist and different mutations can occur even within one infected individual. FIV-infected cats can live symptom-free for years but, due to the virus attacking CD4 lymphocytes, there is a progressive decline in immunity; with some cats eventually developing Feline Acquired Immunodeficiency Syndrome. Clinical signs of FIV infection are often associated with secondary infections due to immunosuppression. However, primary effects of FIV include inflammatory ocular diseases, renal disease and haematology abnormalities. There is no effective treatment for FIV that improves life expectancy, but there are treatment options that may improve clinical signs, along with treatment of secondary infections. There is a vaccine available for FIV in USA, Australia and New Zealand. Many cats with FIV can live long and happy lives if they are managed correctly and receive appropriate healthcare.

Key words: feline immunodeficiency virus, immunodeficiency, retrovirus, antiviral treatment, immunomodulatory therapy

IntroductionFeline immu-nodeficiency virus (FIV) was first described in 1987, in a colony of rescue cats in California, USA, who were showing clinical

signs of immune-deficiency (Pedersen et al. 1987). The clinical signs of FIV infection vary greatly between individual cats yet the disease was the most com-monly reported cause of mortality in adoption centres in the United Kingdom (UK) in one study (Murray at al. 2008). Today FIV remains a source of fear and misunderstanding amongst both owners and veterinary professionals with many FIV-infected cats euthanased at diagnosis. Recent studies demonstrating comparable lifespans between infected and uninfected cats add evidence to opinion that a posi-tive FIV blood test does not need to be an immediate death sentence for a cat and many FIV positive cats can live for several healthy years after diagnosis. Understand-ing how to diagnose FIV and knowing the clinical signs and possible treatments can all help with informed decision mak-ing regarding this disease.

What is FIV?FIV is a retrovirus, part of the Genus called Lentiviruses, named after ‘Lentus’ which is Latin for slow (Figure 1) and is closely related to human immunodeficiency virus

VETcpd - Feline: FIV Update

Helen Bolter BVSc MRCVSHelen graduated from Bristol Veterinary School in 2008 and, in the same year, received an award from Cats’ Protection for a research proposal into blood pressure monitoring in geriatric cats. Having worked in small animal practice for just under a year, Helen went to South Africa and Namibia to work with big cats. Helen currently runs cat-only clinics in the UK. She has an interest in geriatric medicine, having herself re-homed several feline old age pensioners. Helen is also a tutor on International Cat Care’s Cat Professional and Feline Nursing distance education courses.

(HIV). These complex retroviruses contain the important genes gag, pol and env, encoding for capsid protein p24 (impor-tant for diagnosis), reverse transcriptase enzymes (important for the virulence of the virus), and viral proteins (determining viral diversity) respectively. FIV has a high mutation rate because the reverse tran-scriptase enzyme is often inaccurate and creates genetic errors. This leads to the circulation of many heterologous strains, even within a single infected cat. Some of these mutations may lead to changes in virulence, and so the prognosis for each infected cat can vary a great deal.

FIV is found world-wide. There are five distinct variants of the virus, known as clades or subtypes, found in different geographical areas and with significant diversity in the env gene. These five subtypes have been identified based on nucleotide sequence differences or the coding for the viral envelope or poly-merase. Also, within each clade there are genetic variations; some isolates being more pathogenic than others. The five clades are named A through E, with A being the only clade found in the UK and with B being the most common, found in other parts of the world, including Japan and the USA. Interestingly FIV is also found in wild big cat populations, includ-ing lions and puma, with endemic, high prevalence infections reported, and clades different from those affecting domestic cats (Carpenter et al. 1996, Brown et al. 1994).

For Feline Referrals in your area: vetindex.co.uk/felineFor Lab Tests and Equipment:vetindex.co.uk/Lab

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Page 2: Feline immunodeficiency virus: where are we now? · Feline immunodeficiency virus (FIV) is a lentivirus that is most commonly transmitted between cats by biting. Many different strains

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Feline immunodeficiency virus: where are we now?

VETcpd - Feline: FIV Update

How common is FIV around the world? Interestingly the prevalence of FIV seems to remain at similar levels whereas infec-tion with feline leukaemia virus (FeLV) has dropped considerably over the last 10 years due to vaccination uptake.

Studies have demonstrated that the preva-lence of FIV is variable between different populations of cat, with the lowest rates being found in cats appearing healthy and the highest infection rates reported in sick cats (estimates of 1-14% and up to 44% respectively) (Hartmann 1998).

In the UK, prevalence rates vary up to 19% in sick pet cats and 6% in healthy pet cats (Hosie et al. 1998), with a recent study of cats presenting to UK adoption centres showing an overall prevalence of 3.1% (antibody positive) (Murray et al. 2009).

Infection is likely to be higher in free-living cats, for example in Australia a study showed a prevalence of 22% in feral cats (Norris et al. 2007). In general the prevalence in the Asia Pacific region appears amongst the highest internation-ally (Liem et al 2013) with a recent survey of pet cats in Australia revealing a prevalence of 10.4% (Chang-Fung-Martel et al. 2013). A recent study demonstrated a high prevalence in cats in hoarding cases, emphasising the need for testing cats from such environments (Polak et al. 2014).

Risk factors for infection with FIV include illness, male sex and a free-roaming life style, consistent with the main methods of transmission (Hosie et al. 2009).

Transmission of FIVFIV is present in an infected cat’s saliva and transmitted most commonly via a bite. Hence FIV positivity has been associated with aggressive behaviour and the presence of cat bite abscesses and cat bite wounds (Goldcamp et al. 2008).Transmission between cats in stable groups is relatively rare, even with shared access to resources (Litster 2014).

Trans-placental transmission can occur but post-natal transmission via milk is more common. Infection is also possible via blood transfusions, so testing of donor cats is particularly important. Sexual transmis-sion has been experimentally induced, but it is not known whether this is a common route of transmission in natural infections. It is also not known if FIV can be trans-mitted via blood-sucking parasites, but this may be another reason why prophylactic flea control should be recommended.

Figure 1: The FIV virus (red arrow) enters and replicates in lymphocytes (cell on the right of the image), eventually resulting in immunodeficiency.

Pathogenesis of FIV infectionAfter initial infection, FIV multiplies in an infected cat’s immune cells (mainly CD4+ T helper lymphocytes, which are essential for both cell-mediated and humoral immunity, also dentritic cells and macrophages) and cleverly uses the reverse transcriptase enzyme to transcribe its RNA genome into a DNA copy. As mentioned this process frequently results in transcription errors and viral variation that can complicate diagnosis and immune detection. It is this ability to integrate into the cell’s own genome that makes it difficult to treat post infection. A period of

Figure 2: A cat with FIV suffering repeated skin infections, in this case with Demodex cati. Photo courtesy of International Cat Care.

latency follows acute infection where the cell contains proviral DNA but does not produce virus particles to infect other cells, presumably due to an effective immune response controlling the infection. This period may last months to years, or be lifelong. The symptomatic period of FIV infection is associated with a decline in CD4+ lymphocyte numbers, reducing the CD4:CD8 T lymphocyte ratio and leading to clinical signs of acquired immunodefi-ciency syndrome. Response to infection is likely to be influenced by the virulence of the virus itself, with the emergence of viral phenotypes with affinity for certain cellular receptors marking the onset of immunodeficiency and progression of disease (Beczkowski et al. 2014).

Clinical signs of FIVFIV infection results in progressive immune function deterioration, yet these changes do not necessarily result in clini-cal signs in the cat. The clinical course of FIV infection in cats is not as predictable in cats as HIV is in humans (Liem et al. 2013) with variable periods of time when the cat remains asymptomatic, with some cats never developing disease associated with reduced immune function.

Immediately after initial infection, there is an ‘acute phase’ where the cat may present with subtle and often unnoticed signs of lethargy, lymphadenopathy, anorexia and pyrexia. A neutropenia may be detected.

The later clinical signs associated with FIV are non-specific and are usually not a direct effect of the virus itself, but are due to secondary infections that occur as a consequence of the immunosuppression FIV causes. Examples include calicivirus, herpes virus, various bacteria, parasites and fungi, all taking advantage of the cat’s sup-pressed immune system (Figure 2). FIV infection should be suspected if unusual infectious agents or repeated infections are diagnosed, or infections fail to respond well to treatment.

Clinical syndromes associated directly with FIV itself include neoplasia, com-monly lymphoma; inflammatory ocular diseases such as uveitis and chorioretinitis; neurological diseases such as dementia or seizures; stomatitis (Figure 3) and haematological abnormalities such as neutropaenia, thrombocytopaenia and, in advanced cases, non-regenerative anaemia.

Renal disease has been associated with FIV infection but a recent study showed proteinuria but not azotaemia was

Figure 3: FIV can cause stomatitis, perhaps due to co-infection with other pathogens such as feline calicivirus. Photo courtesy of International Cat Care.