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Feline Immunodeficiency Virus


The feline immunodeficiency virus or FIV is the cause of an infection that is both widespread in domestic cats but also particularly unknown. Many owners do not know the status of their animal or even the existence of such pathology. Yet FIV is found on every continent and can affect any cat, showing symptoms only years after infection. It is estimated that around 5% of cats in the UK and around 7% of cats in France are tested positive. On a European scale, they represent several million seropositive domestic felines. There is currently no vaccine against the FIV virus. Care is only symptomatic but can be insufficient, inappropriate and can lead to permanent suffering in individuals as well as helplessness on the part of owners and veterinarians. The diagnosis of FIV can lead some owners to abandon their animals or even require their euthanasia.



Overview of the virus


The FIV virus was isolated for the first time in 1986 in Petaluma in California (USA) by professors Niels PEDERSEN and Janet YAMAMOTO when a community of cats with a high mortality rate presented in the majority of individuals severe chronic infections and multiple associated with a profound immune deficiency. The term FIV did not appear until 1988 after clinical studies demonstrated a correlation between this viral infection and the immunodeficiency of affected cats. Several studies have isolated the virus from cats, lions, tigers, lynxes, pumas, leopards, snow leopards, jaguars, and cheetahs. Genetic differences of the virus between species may suggest the existence of an ancestor of FIV that appeared before felids diverged into different species three to six million years ago. Despite much research since its discovery, the feline immunodeficiency virus remains an enigma in the scientific and veterinary world.

The FIV virus is a Lentivirus, from the Latin lentus "slow", of the Retroviridae family, the main characteristic of which is a long incubation period. Its activity is cytopathogenic, in other words it destroys the cells that it infects. These cells are mainly B lymphocytes, T lymphocytes, macrophages, and dendritic cells which are all actors in the immune response. Infection by FIV therefore causes an immune deficiency, a predisposition to infections by opportunistic pathogens or even by the appearance of autoimmune diseases. The cells targeted by FIV have on their surface specific CD134 and CXCR4 receptors which form the virion insertion sites during the first stage of the viral cycle. The first sites of viral replication are the lymph nodes, the spleen and the bone marrow; then the infected monocytes and lymphocytes spread to multiple sites in the host, including the brain, lungs and joints.



FIV follows two strategies against the host's immune response:

- A latent infection, which can extend over several years

- Genetic variability

Some studies have observed several variations of FIV according to cat populations and have been able to define five main types of viruses that are genetically distinguished. The different types of viruses have been classified into subspecies A, B, C, D, and E which correspond to different global locations. Research carried out in 2004 by researchers REGGETI and BIENZLE also demonstrated the existence of intermediate subtypes formed by recombination of several subtypes present in the same region, thus creating new viruses with different properties and pathogenies.



Transmission


Saliva: The FIV virus is present in the saliva of cats, which represents the main natural transmission. The virus is present in the salivary glands as early as the first week after infection, suggesting that they may represent an early site for FIV migration or replication. However, the virus from saliva remains difficult to isolate, which indicates that the quantity of infecting virus is low. The presence of viral RNA in saliva, on the other hand, suggests the presence of infected cells, cellular debris and free virions that have migrated from blood vessels to the oral cavity. Transmission would therefore be through blood but via salivary transport. Under natural conditions, the most common contamination is during fights, a single deep bite can be enough to transmit the virus. Transmission through licking wounds, mutual grooming or sharing food bowls is still questioned, but the hypothesis has not been ruled out.


In Utero : Transmission of the virus from infected cats to their kittens has been demonstrated experimentally but appears to be rare in naturally infected animals. FIV in pregnant mothers can cause abortions, delayed fetal development, premature births, and increased neonatal mortality rates. When the transmission of the virus has taken place, the seropositive kitten sees its chances of viability reduced. Kittens with the virus in utero will usually be smaller and will experience developmental difficulties even as adults.


Postnatal : Transmission of FIV after the kitten's birth is possible through ingestion of colostrum and infected breast milk but remains relatively rare. Several studies have shown that transmission of FIV from mother to kittens is possible during the terminal phase of the infection. During the asymptomatic phase, transmission does not take place. FIV was isolated in 77.8% of colostrum samples and in 36% of milk samples from females in symptomatic phase of infection.


Venereal : The opinion of researchers on this mode of transmission is still very divided, while some studies claim that sexual transmission of FIV is rare but quite possible, others argue that the virus cannot be spread via this process. The semen of infected male cats does contain viral cells, however their number is lower in the semen than in the blood, which could imply that the virus present in the seminal fluid may come from sources other than the infected seminal cells.



Pathogenesis


The acute phase, primary infection or stage I appears in the first months after infection and lasts three to ten days. The integration of the virus into the host genome then takes place, leading to a persistent infection. The first clinical signs to appear are fever often associated with neutropenia, pharyngitis, generalized and persistent lymphadenopathy, more or less marked weight loss, depression, dermatitis, diarrhea and conjunctivitis. Mortality is low at this stage of infection, it is less than 10% of cats in the acute phase, however it increases sharply in the case of co-infection with FeLV.


The asymptomatic phase or stage II corresponds to an average period generally between 5 years and 10 years or sometimes more in certain individuals. This is the longest stage of infection. This phase is characterized by a strong immune response which allows control of viral replication and therefore the absence of infection or opportunistic diseases. There are usually no symptoms associated with this phase which makes it difficult to diagnose, but it is still possible to isolate the virus.


The phase of persistent generalized lymphadenopathy or stage III is not always present in cats. It is characterized by a generalized increase in the size of the lymph nodes and is often found associated with recurrent fevers, weight loss and changes in animal behavior. This viral step usually goes unnoticed.


The ARC phase (AIDS-Related Complex) or stage IV is characterized by the appearance of chronic pathogenic infections associated with general signs. Chronic secondary infections are often localized in the oral mucous membranes in the form of persistent gingivitis and stomatitis, in the respiratory or ocular system in the form of recurrent rhinitis and conjunctivitis, or in the skin in the form of persistent abscesses. These symptoms gradually worsen. The death rate is sharply higher at this stage of infection, especially in older and vulnerable individuals.


The AIDS phase or stage V constitutes the terminal stage of the disease. Once declared, it does not allow any further improvement. This stage has been observed in 5 to 10% of cats infected with FIV, clinically ill and presented to a veterinarian. The immune system is considerably weakened, which implies the appearance of repeated infections with opportunistic germs associated with general signs of increasing severity. In addition to infections, the cat will present with severe neoplastic and neurological damage. The animal on treatment will usually become resistant to the antibiotics and will die. The average survival time of this last viral phase is generally less than a year despite the treatments.



Symptoms / associated pathologies



Gingivitis: It is an infection of the gums. The mucous membranes become red, swollen, and very painful which results in loss of appetite, bad breath and difficulty eating. If left untreated, the gradual detachment of the gums causes tooth loss, and the lesion resulting from this tooth loss can become a source of bacterial infection.


Stomatitis: This is an inflammation of the oral cavity. Stomatitis usually begins in the pharyngeal region and spreads rostrally, especially along the maxillary teeth. The origin can be infectious, organic or metabolic, but whatever the cause, secondary bacterial infections are a major contributor to the lesions. When these are chronic, they usually end with tooth extraction.


Respiratory infection: The upper respiratory tract is most often affected and the animal quickly exhibits symptoms such as cough, mucous to mucopurulent discharge, sneezing, increased breath sounds or crackles, chronic tracheal involvement and difficulty to breathe.


Enteritis: This is inflammation of the small intestine that can sometimes be associated with gastritis which more generally results in inflammation of the lining of the lining of the digestive tract. The main symptoms are frequent vomiting and diarrhea, and they often accompany inflammation of the oral cavity. Almost one in four cats with FIV has chronic enteritis and diarrhea.


Nephropathy: This is a kidney disease whose causes can be multiple: diabetes, infections, autoimmune diseases, hypercalcemia, inflammation. It is a fairly common symptom for cats with FIV and which would be found in about 11% of cases. A study suggests that the virus could replicate in kidney cells and therefore have a direct role in the kidney damage seen in FIV cats. The main clinical signs are polyuria, polydipsia, weight loss, nausea, depression and sometimes a significant increase in the size of the kidneys.


Lymphadenopathy: This is a pathological condition of the lymph nodes which results in an increase in their palpable volume and inflammation, generally accompanied by more or less marked pain. Some symptoms arise from these compression phenomena such as coughing, difficulty breathing and signs of chest pain. Follicular hyperplasia of the spleen may be present, hyperplasia of the lymphoid follicles in the intestine, or of the liver and bone marrow, thymus gland, thyroid glands, kidneys and eyes.


Neurological dysfunctions: This is damage to the nervous system which manifests itself in various clinical signs of varying severity. These neurological dysfunctions are often typical of the stage IV. FIV is a lentivirus neurotrope and can be directly associated with nervous pathologies, it enters the brain during the primary infection phase. The clinical signs are changes in behavior, dementia, sleep disorders, habitual aggressiveness, loss of control over urination and defecation, but also encephalitis, motor and balance disorders, ataxia, faintness, seizures, nystagmus, hypersensitivity to touch and noise, impaired hearing and visual potential, epileptic seizures, delayed photomotor reflexes, anisocoria, facial asymmetries or even paralysis.


Eye damage: These are damage or lesions affecting the eyes of the animal and may be completely benign or much more serious, including blindness. The main symptoms of eye disease are redness around and inside the eyeball, discharge, scabs, swelling and itching, sometimes leading to partial or complete disorientation of the animal.


Neoplasia: This is an abnormal cell proliferation that forms a tumor or cancer. Neoplasms of the skin are common in cats, the most common condition of which is fibrosarcoma, which develops in subcutaneous tissue and spreads intramuscularly. Several studies have shown that an FIV positive cat is 6 times more likely to develop lymphoma than a healthy cat.



Prognosis


Lack of knowledge about FIV makes the prognosis difficult. It depends on the animal's past, its environment and the care provided during its life. If the owner watches for the onset of symptoms, maintains a consistent and slightly elevated weight for prevention, takes their pet to the vet regularly for routine visits, limits the stress on the animal, then the chances of the cat maintaining itself at the asymptomatic stage are relatively large. The animal may never even develop a serious illness related to the virus.



Prevention


Isolation: One of the most common recommendations made by vets is to isolate the seropositive individual to avoid contact with a healthy cat. In an already established cattery, the risk of contamination is lower because the hierarchy is installed, the quarrels are less frequent and generally not very violent. The introduction of a new cat is not recommended since the risk is high, conflicts are likely to be responsible for contamination. In addition, it is recommended to strictly isolate the FIV cat indoors to avoid contamination of cats outdoors but also to minimize the risk of infections that they could contract.


Sterilization: Sterilization of the cat with FIV is essential, whether male or female. Indeed, males are more prone to contracting the virus through conflicts. Females are less affected by the risk of infection, but they can occasionally transmit the virus to their kittens and are not immune to hierarchical conflicts.


Vaccination against opportunistic diseases: Many veterinarians recommend the complete vaccination of seropositive cats in order to restrict the onset of opportunistic infections, especially against leukosis. However, some reports have shown that the vaccine works adversely, the reactivity of the already weakened immune system is not sufficient to counter the foreign pathogen. It is essential to know the stage of infection before proceeding with the vaccination. In fact, at a primary stage when the immune system is initially very active, it is undesirable to introduce another pathogen that could further upset homeostasis and weaken the individual. It is preferable in this case to wait for the asymptomatic stage of infection, since the virus is almost inactive it is much easier for the immune system to defend the body and activate the memory cells. It is essential during this step to carry out a regular vaccination in order to protect the animal as much as possible, while avoiding over-vaccination. In the terminal stage of infection, it is best to vaccinate only if clearly necessary.


Vaccination against FIV: Fel-O-Vax® FIV is the only vaccine marketed. It is available in the United States, Australia, New Zealand and Japan but is not marketed in Europe due to its many controversies. First of all, vaccination with Fel-O-Vax® FIV only provides partial protection and therefore does not protect against all strains of the virus. In addition, the risk of sarcoma would be amplified in the presence of the adjuvant of the vaccine. Finally, similar to the vaccination against opportunistic diseases, the anti-FIV vaccination would call on the immune system in order to cause an increase in the replication of the virus.



Treatments


There is currently no cure to destroy the feline immunodeficiency virus.


The only care available is to improve the animal's quality of life by providing allopathic or alternative symptomatic treatments. Specific antiviral treatments are used to slow the progression of the disease. However, the intervention is particularly delicate as the virus replication cycle must be interrupted by starting treatment at the end of the asymptomatic phase which is marked by a consequent decrease in the number of CD4 and CD8. Non-specific antivirals are also used, the most common molecules of which for the treatment of FIV cats are interferons. In the most serious cases, only palliative treatment is possible to support the animal at the end of its life by reducing viremia and providing it with maximum comfort. This treatment generally consists of reducing the pain resulting from opportunistic infections that are too developed to be treated. Glucocorticoids are steroidal anti-inflammatory drugs with antipyretic and analgesic action and are also involved in protein and carbohydrate metabolism. They have long been used for the symptomatic treatment of FIV in the past but are not recommended today because they cause an increase in viraemia. However, they are sometimes inevitable.



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