Synopsis of Feline leukemia virus infection and its relationship to feline infectious peritonitis

21.5.2021
Niels C. Pedersen, DVM, PhD
Original article: Synopsis of Feline leukemia virus infection and its relationship to feline infectious peritonitis

Basic facts - Feline leukemia virus (FeLV) is a retrovirus related to the murine leukemia virus that existed among feral cats for tens of thousands of years before its discovery in 1964 (Jarrett et al., 1964). FeLV infection occurs mainly in cats less than 3-8 years of age (Pedersen, 1998, 1991). Cats in the asymptomatic stage of the infection are the main source of infection. The virus is secreted in all secretions and bodily secretions and spreads by close contact (Pedersen et al., 1977). FeLV infection usually occurs in nature after cats are old enough to socialize, and the primary phase of the infection is either asymptomatic or transient and ends with a long-lasting immune response in 95% or more cats. Only a small proportion of infections in nature lead to chronic viremia. FeLV-associated diseases occur predominantly in a small group of cats with persistent infection.
FeLV disease in feral cats did not arouse increased interest prior to its discovery, and any associated mortality remained unnoticed among the spectrum of diseases that affect feral cats. What we know about the pathogenesis of FeLV infection in feral cats therefore originally came from studies conducted in the 1970s and 1980s on groups of domestic cats and laboratory infections (Review Pedersen, 1998, 1991).

Epizootiology - FeLV appears to have inadvertently migrated from the wild to the domestic cat population sometime before the 1960s, and the incidence has increased rapidly since then. The first indications that the virus may be behind the disease came in 1964 with the identification of intracellular particles resembling the murine leukemia virus in the cat's home with multiple cases of lymphosarcoma (Jarrett et al., 1964). Our understanding of the severity of FeLV infection and its relationship to diseases other than lymphosarcoma began in 1969 in research laboratories (Hardy et al., 1969). The main spectrum of FeLV-related diseases arose from the commercial application of the Indirect Fluorescence Antibody Test (IFA) for the detection of viremic cats, beginning in 1972 (Hardy, 1973; Hardy and Zuckerman, 1991). Rapid domestic ELISA-based FeLV assays followed (Lutz et al., 1979).

FeLV was retrospectively identified as the leading cause of domestic cat disease in the 1960s and prospectively in the 1970s and 1980s. What caused the panzootic of FeLV infection and diseases in domestic cats? It was later found that a human-controlled environment with a large population of cats, especially where young kittens were in contact with older infected kittens and cats, proved to be ideal for cat-to-cat transmission. The severity of these exposures, along with young age (Hoover et al., 1976) and other environmental stressors, has significantly increased the incidence of persistent infections compared to transient infections (Pedersen et al., 1977). While only a small percentage of cats in the wild become permanently viremic, one-third or more cats exposed in a controlled laboratory environment have developed persistent viremia.

The end of the FeLV panzootic came with extensive "testing and segregation" of viremic cats, as documented by Weijer et al. (1986). Testing and segregation were later supplemented by effective vaccines. Remarkably, FeLV infection is no longer the leading cause of disease in households with multiple cats. Again, it exists as a natural infection, with positivity only in 1-5% wild cats. However, several viremic cats, especially younger ones, continue to appear among cats moved from the wild to shelters and temporary homes.

Pathogenesis - primary FeLV infection is largely insignificant in nature and terminated by a strong immune response and lifelong immunity (Review Pedersen, 1991). However, if the extent of exposure is large enough and / or the feline's immunity is reduced in some way, primary and transient disease may occur. This stage can be manifested by fever, generalized lymphadenopathy, low platelet and WBC counts, and mild anemia. This stage is often followed by long-lasting and largely asymptomatic viremia lasting months and years. Cats with persistent FeLV infection eventually develop several primary and secondary diseases, which are usually fatal. The usual mortality estimate for viremic cats is around 50% per year (Pedersen, 1988), which means that only 12.5% of them will survive after three years. Because infection in nature occurs mainly in younger cats and most of them die within 3 years, few cases of FeLV infection are observed in nature in cats older than 5-8 years.

Primary FeLV diseases are associated with various mutants of the infecting strain and include aplastic anemia, various myeloproliferative disorders, and lymphoma, which is usually generalized, ocular, or neurological (Summary Pedersen 1988, 1991). FeLV-associated secondary disease is caused by several common feline infectious agents, which are usually not very pathogenic, but which are exacerbated by suppression of FeLV-associated T cell immunity.

Relationship between FeLV and FIP infection - One-third to one-half of cats with FIP have been found to be infected with FeLV during the 1970s and 1980s (Cotter et al., 1973; Pedersen et al., 1977). The association between the two infections has been shown when young laboratory cats with enzootic feline enteric coronavirus (FECV) infection were bred with FeLV carriers (Pedersen et al., 1977). When these young cats became permanently infected with FeLV, their coronavirus antibody titers began to increase and clinical signs of FIP appeared within a few weeks or months. FIP occurred in only one-third of cats with viremia of FeLV, and two-thirds of cats that became immune to FeLV had no cases of FIP. In a later study, cats were chronically infected with a laboratory strain of feline immunodeficiency virus (FIV) experimentally infected with FECV (Poland et al., 1996). Two of the 19 cats in the chronic immunosuppressive stage of FIV infection developed FIP, while none of the 20 FIV uninfected "roommates" became ill. Studies similar to those with FeLV and FIV immunosuppression were important in concluding that FIP virus (FIPV) was a common FECV mutant and minimal pathogen in healthy immunocompetent cats.

What does FeLV infection mean for the treatment of FIP? I admit that I am not in favor of FIP treatment in FeLV-positive cats. We know that FeLV infection induces the type of immunosuppression that leads to the development of FIP. I also suspect that successful treatment with FIP antivirals such as GS-441524 is based on restoring the protective immune response to FIPV. If true, FeLV-induced immunosuppression may interfere with FIPV immunity and reduce the cure rate in GS treatment, or interfere with any long-term protective immunity elicited by successful antiviral therapy. Two other problems with the treatment of such cats need to be considered. Breeding FeLV-infected cats causes financial and physical difficulties in terms of routine veterinary care and quarantine of susceptible cats. It is also known that only 10% cats infected with FeLV survive for more than three years. These facts raise questions about the best use of the resources of temporary / rescue groups and individuals - for cats with only FIP, cats with other treatable diseases or for healthy cats waiting for home?

Conclusion - Foster parents / rescuers are unlikely to choose not to treat FIP in FeLV positive cats. However, the decision to treat FIP in such cats must be based primarily on the accuracy of the initial FeLV test. About 5 out of 100 positive in-house FeLV ELISAs in a healthy cat population will be false positive. If FeLV is present in the 1% street cat population, false positive results will be five times more common than true positives. Therefore, it is important that positive ELISAs be confirmed by another test, such as PCR. Owners should, whenever possible, ensure that these cats do not have other FeLV-related diseases, such as aplastic anemia, lymphoma or myeloproliferative disorders. Cat owners who opt for GS treatment should also share the short-term and long-term results of their efforts in order to obtain a better prognosis in this FIP group.

References

• Cotter SM, Gillmore CE, Rollins C. 1973. Multiple cases of feline leukemia and feline infectious peritonitis in a household. J Am Vet Med Assoc 162:1054-1058.
• Hardy WD Jr., et al. Feline leukemia virus: occurrences of viral antigen in the tissues of cats with lymphosarcoma and other diseases. Science 1969, 166:1019-1021. 
• Hardy WD Jr. Horizontal transmission of feline leukemia virus in cats. Nature 1973, 244:266269. 
• Hardy WD Jr., Zuckerman EE. Ten-year study comparing enzyme-linked immunosorbent assay with the immunofluorescent antibody test for detection of feline leukemia virus infection in cats. J Am Vet Med Assoc. 1991, 199:1365-73.
• Hoover EA, et al. Feline leukemia virus infection: Age-related variation in response of cats to experimental infection. J Natl Cancer Inst. 1976, 57:365-369. 
• Jarrett WFH, et al., Leukemia in the cat. A virus-like particle associated with leukemia (lymphosarcoma). Nature 1964, 202:567-56.
• Lutz H, et al. The Demonstration of Antibody Specificity by a New Technique. The Gel
• Electrophoresis-Derived Enzyme-Linked Immunosorbent Assay (GEDELISA) and its Application to Antibodies Specific for Feline Leukemia Virus. J Histochem Cytochem. 1979, 27: 1216-1218.
• Pedersen NC. Feline Infectious Diseases. American Veterinary Publications, Inc., Goleta, CA, USA, 1988.  
• Pedersen NC. Feline leukemia virus infection. In: Feline Husbandry. Disease and management in the multiple-cat environments. American Veterinary Publications, Inc., Goleta, CA, USA, 1991, pp210-228. 
• Pedersen NC, Theilen G, Keane MA, Fairbanks L, Mason T, Orser B, Che CH, Allison C. 1977. Studies of naturally transmitted feline leukemia virus infection. Am J Vet Res 38: 1523–31.
• Poland AM, Vennema H, Foley JE, Pedersen NC. 1996. Two related strains of feline infectious peritonitis virus isolated from immunocompromised cats infected with feline enteric coronavirus. J Clin Micro 34: 3180–3844. Weijer K, de Haag U, Osterhaus A. 1986. Control of feline leukemia virus infection by a removal program. Vet Rec, 119, 555–556.