Diseases associated with spontaneous feline leukemia virus (FeLV) infection in cats

More than 2000 cats sent for necropsy in order to provide a diagnosis were investigated immunohistologically using paraffin sections for the presence of a persistent infection with feline leukemia virus (FeLV). The spectrum of neoplastic and non-neoplastic diseases associated significantly with FeLV infection was determined statistically. Three-quarters of the cats with persistent FeLV infections died of non-neoplastic diseases and about 23% died of tumors, nearly exclusively those of the leukemia/lymphoma disease complex. A strong association with liver degeneration, icterus and a FeLV-associated enteritis was found in addition to the known association with non-neoplastic diseases and conditions such as anemia, bacterial secondary infections and respiratory tract inflammations due to the immunosuppressive effect of FeLV, hemorrhages and feline infectious peritonitis. Surprisingly, diseases and conditions like feline infectious panleukopenia, enteritis (of other types than FeLV-associated enteritis and feline infectious panleukopenia), glomerulonephritis, uremia and hemorrhagic cystitis were not associated with persistent FeLV infection. Another unexpected finding was that most pathogenic infectious agents demonstrated in the cats were not FeLV-associated either. Thus, immunosuppression due to FeLV infection seems to make the animals susceptible to certain pathogenic infectious agents, but not to the majority.     

Detection of feline immunodeficiency virus infection in bone marrow of cats.

Natural or experimental feline immunodeficiency virus (FIV) infection in cats is often associated with hematologic abnormalities which are similar to those observed in human immunodeficiency virus (HIV) infected patients. To determine if cells in bone marrow are infected with FIV and whether severity of hematopoietic disorder is correlated with the level of viral infection, bone marrow tissues from ten experimentally and two naturally FIV infected cats were examined by in situ hybridization for presence of FIV RNA. Seven of the 12 FIV infected cats were also naturally or experimentally coinfected with feline leukemia virus (FeLV). FIV RNA was detected mainly in megakaryocytes and unidentified mononuclear cells in the bone marrow of cats that were sick and had marrow hypercellularity and immaturity. These included all cats in the acute phase of FIV infection and two of seven long term FIV infected cats. One long term FIV infected cat with lymphosarcoma was also positive for FIV RNA in bone marrow cells. The other four long term FIV infected cats were relatively healthy, with normal bone marrow morphology, and were negative for FIV infected cells. Bone marrow from three non-infected and two cats infected with FeLV alone were also negative for FIV RNA by in situ hybridization. We concluded that megakaryocytes and mononuclear cells were targets of the viral infection and that the presence of FIV RNA in cells of the bone marrow correlated with marrow hypercellularity and immaturity, and severity of illness.     

Diagnosis of feline leukemia virus and feline immunodeficiency virus infections

Feline leukemia virus is an oncogenic retrovirus that can result in a wide variety of neoplastic and non-neoplastic diseases, including immunosuppression. Diagnosis of FeLV infection can be achieved by several methods, including virus isolation; IFA assay of a peripheral blood smear; and detection of a viral protein (called p27) by ELISA testing of whole blood, plasma, serum, saliva, or tears. Commercially available ELISA kits have revolutionized FeLV testing and have become very popular as "in-house" procedures. This article discusses the interpretation of ELISA results and compares them with IFA assay findings. Feline immunodeficiency virus is a lentivirus that causes immunosuppression, but not neoplasia, in cats. It originally was called feline T-lymphotropic lentivirus. Differentiating FIV infection from the immunosuppressive type of FeLV infection requires virus isolation or serology. The most rapid method for diagnosis of FIV infection is ELISA testing for antiviral antibody.     

Frequency and significance of feline leukemia virus infection in necropsied cats

Feline leukemia virus (FeLV) infection was diagnosed immunohistologically on paraffin-embedded tissues obtained from 1,095 necropsied cats. Significant association of FeLV infection was demonstrated by chi 2 and Fisher's tests with various conditions and diseases (ie, anemia, tumors of the leukemia/lymphoma complex, feline infectious peritonitis, bacterial infections, emaciation, FeLV-associated enteritis, lymphatic hyperplasia, and hemorrhage). Unexpected findings associated with FeLV infection were icterus, several types of hepatitis, and liver degeneration. A negative association with FeLV infection was found for most parasitic and viral infections, including feline panleukopenia. Neither positive nor negative associations were established for FeLV infection and most forms of nephritis, including severe glomerulonephritis. Feline leukemia virus-infected cats were significantly (Kruskal-Wallis test) older than were FeLV-negative cats with the same nonneoplastic FeLV-associated diseases.     

Steroid-responsive neutropenia in a cat with progressive feline leukemia virus infection

An 8-month-old female domestic shorthair cat was presented to the Animal Medical Center with anorexia, lethargy, and mild gastrointestinal signs. A CBC revealed a profound neutropenia, and serologic testing with an in-house test kit (SNAP FIV/FeLV Combo, IDEXX) was positive for feline leukemia virus (FeLV) antigen. Serial hematologic examinations during hospitalization showed a persistent neutropenia with occasionally severe anemia and thrombocytopenia. Prednisolone administration afforded complete hematologic remission within 3 days. Four weeks after the premature discontinuation of prednisolone, the patient relapsed; however, complete and prolonged hematologic remission was achieved after prednisolone was re-induced. Bone marrow aspiration cytology was consistent with immune-mediated destruction of the mature myeloid cells. steroid-responsive (likely immune-mediated) cytopenias rarely occur in cats with progressive FeLV infection. Although only a few cases of FeLV-positive, severely neutropenic cats that responded to immunosuppressive therapy have been reported, this case highlights that a grave prognosis should not always be given to these FeLV-positive cats.     

Therapeutic effects of recombinant feline interferon-omega on feline leukemia virus (FeLV)-infected and FeLV/feline immunodeficiency virus (FIV)-coinfected symptomatic cats

The clinical efficacy of a recombinant feline interferon, rFeIFN-omega, was evaluated for the treatment of cats presented with clinical signs associated with feline leukemia virus (FeLV) infection and FeLV/feline immunodeficiency virus (FIV) coinfection in the field. In this multicentric, double-blind, placebo-controlled trial, 81 cats meeting the inclusion criteria were randomly placed into 2 groups and treated subcutaneously with rFelFN-omega (1 million [M]U/kg per day) or placebo once daily for 5 consecutive days in 3 series (day 0, 14, 60). The cats were monitored for up to 1 year for clinical signs and mortality. During the initial 4-month period, interferon (IFN)-treated cats (n = 39) had significantly reduced clinical scores compared with placebo (n = 42), with all cats having received concomitant supportive therapies. Compared with the control, the IFN-treated group showed significantly lower rates of mortality: 39% versus 59% (1.7-fold higher risk of death for controls) at the 9-month time point and 47% versus 59% (1.4-fold higher risk of death for controls) at the 12-month time point. The IFN treatment was associated with minor but consistent improvement in abnormal hematologic parameters (red blood cell count, packed cell volume, and white blood cell count), apparently underlying the positive effects of IFN on clinical parameters. These data demonstrate that rFeIFN-omega initially has statistically significant therapeutic effects on clinical signs and later on survival of cats with clinical signs associated with FeLV infection and FeLV/FIV coinfection.     

How molecular methods change our views of FeLV infection and vaccination

FeLV was discovered 40 years ago and vaccines have been commercially available for almost two decades. So far, most FeLV pathogenesis and vaccine studies were conducted assaying parameters, such as virus isolation and antigen detection. Accordingly, regressive infection was characterized by transient or undetectable viremia, while persistent viremia is typically observed in cats with progressive infection. Using real-time polymerase chain reaction assays, the spectrum of host response categories to FeLV infection was recently refined by investigating proviral and plasma viral RNA loads. Cats believed to be immune to FeLV infection were found to turn provirus-positive after virus exposure. Moreover, efficacious FeLV vaccines were found unable to prevent provirus-integration and minimal viral replication. Remarkably, no difference was found in initial proviral and plasma viral RNA loads between cats with different infection outcomes. Only subsequently, the infection outcome is associated with FeLV loads. FeLV provirus was found to persist for years; reoccurrence of viremia and disease development was observed in some cats. Thus, aviremic provirus-positive cats are FeLV carriers and, following reactivation, may act as an infection source. However, integrated viral DNA may also be essential for solid protection and long-lasting maintenance of protective immunity. In conclusion, real-time TaqMan PCR and RT-PCR assays are highly sensitive and specific. They yield a more sensitive measure for FeLV exposure than antigen detection, virus isolation or immunofluoresence assays. We recommend the use of real-time PCR assays to identify FeLV exposed cats, particularly in catteries, and investigate obscure clinical cases that may be FeLV-associated. The use of sensitive molecular methods will contribute to a more in-depth understanding of the FeLV pathogenesis.     

Immunogenicity and Efficacy of a Commercial Feline Leukemia Virus Vaccine

Twenty young adult specific pathogen-free cats were randomly divided into two groups of 10 animals each. One group was vaccinated with two doses of feline leukemia virus vaccine according to the manufacturer's recommendations. All 20 cats were challenge exposed oronasally (4 times over a 1-week period), beginning 3 weeks after immunization, with a virulent subgroup A strain of FeLV (CT600-FeLV). The severity of the FeLV infection was enhanced by treating the cats with methylprednisolone acetate at the time of the last FeLV exposure. Ten of 10nonvaccinated cats became persistently viremic compared with 0/10 of the vaccinates. ELISA antibodies to whole FeLV were present at high concentrations after immunization in all of the vaccinated cats, and there was no observable anamnestic antibody response after challenge exposure. ELISA antibodies to whole FeLV appeared at low concentrations in the serum of nonvaccinated cats after infection but disappeared as the viremia became permanently established. Virus neutralizing antibodies were detected in 3/10 vaccinates and 0/10 nonvaccinates immediately before FeLV challenge exposure, and in 8/10 vaccinates and 1/10 nonvaccinates 5 weeks later. Although vaccination did not consistently evoke virus neutralizing antibodies, it appeared to immunologically prime cats for a virus-neutralizing antibody response after infection. Active FeLV infection was detected in bone marrow cells taken 14 weeks after infection from 10/10 nonvaccinates and 0/10 vaccinates. Latent FeLV infection was not detected in bone marrow cells from any of the vaccinated cats 14 weeks after challenge exposure.     

Study of feline leukemia virus immunity.

Fifteen specific-pathogen-free cats were experimentally infected with FeLV; 8 cats recovered after transient or nondetectable viremia, and 7 cats became persistently viremic. Four additional cats served as noninfected controls. Antibodies to whole FeLV (ELISA and immunoblot [western] analysis), antibodies to fixed FeLV-infected cells, and virus-neutralizing antibodies were monitored for as long as 3 years after infection. As a group, cats that recovered after acute infection developed higher titer of these various antibodies than did cats that became persistently viremic. However, specific combination or titer of antibodies was not always found in recovered cats or in persistently viremic cats. Six cats that had recovered from acute FeLV infection nearly 3 years earlier were reinfected with the same virus. Three of the cats appeared to be resistant to reinfection, 2 cats became transiently viremic, and 1 cat became persistently viremic. Slight and transient anamnestic ELISA-detectable antibody response to whole virus was seen after reinfection; immunofluorescence- and western blot-detectable responses were not greatly enhanced. Five FeLV-recovered cats were monitored for 2 years; FeLV infection spontaneously recurred in 1 cat.     

Feline haemobartonellosis: clinical, haematological and pathological studies in natural infections and the relationship to infection with feline leukaemia virus

Haemobartonella felis infection was demonstrated in 38 cats which could be divided into four groups as follows: group A, feline leukaemia virus (FeLV) free cats with H felis infection alone; group B, FeLV free cats with H felis infection and other clinical conditions; group C, FeLV positive cats with H felis infection but no clinical manifestation of FeLV related or any other intercurrent disease; and group D, FeLV positive cats with H felis infection and clinical manifestations of FeLV related or other diseases. Cats in group A were healthy carriers of the infection and none was anaemic, whereas some in group B had clinical haemobartonellosis and anaemia. This anaemia was mainly mild, normocytic and normochromic. Most of the cats in group C and all in group D were more severely ill and anaemic, the anaemia usually being macrocytic and hypochromic. Splenomegaly occurred only in groups C and D. Treatment with tetracyclines did not eliminate H felis from any of the cats and blood transfusions were ineffective in promoting long term recovery from anaemia in cats with intercurrent H felis and FeLV infections. The findings in the cats in groups C and D were further compared with those in a fifth group of cats which were infected with FeLV but free of H felis.     

Giant Cell Dermatosis in FeLV-positive Cats

Abstract— Giant cell dermatosisis is reported in six cats with evidence of concurrent feline leukemia virus (FeLV) infection. Scaling, crusting and alopecia, accompanied by pruritus, affected the head and/or face predominantly in most cats; generalized skin disease developed in one cat. Histologically, giant keratinocytes resembling syncytial cells were found in the epidermis and superficial hair follicles, and were accompanied by dyskeratosis, pustules and ulcers. Immunohistochemical staining revealed FeLV antigen in the giant cells and adjacent keratinocytes. FeLV infection may have led to neoplastic alteration of the keratinocytes through recombination with host oncogenes
Resumen  Este artículo se basa en seis gatos con dermatosis de las células gigantes infectados con el virus FeLV. Éstos animales presentaban escamas y costras, así como pérdida de pelo y picor en las regiones de la cabera y cara, predominantemente. Tan solo uno de los gatos desarrolló una dermatosis generalizada. En el exámen histológico se demostró la presencia de keratinocitos gigantes con semejonza a las células sinticiales localizados en la epidermis y folículos pilosos superficiales, acompañados de disqueratosis, pústulas y ülceras. Las finturas histo-inmunológicas demostraron el antígeno FeLV en las células gigantes y keratinocitos adyacentes. La injeccion con el virus FeLV pudo haber conducido a la alteración neoplástica de los keratinocitos a través de la recombinación con los oncogenes del hospedador.     

Husbandry practices for cats infected with feline leukemia virus or feline immunodeficiency virus.

Cats that are persistently infected with FeLV or feline immunodeficiency virus but are not manifesting clinical signs of disease are at risk for developing a wide variety of immunosuppressive, degenerative, or neoplastic diseases. Infected cats should be isolated to prevent transmission of virus to healthy cats, and to protect infected cats from exposure to pathogens that can cause life-threatening secondary infections. Iatrogenic transmission of virus from infected cats in isolation to healthy cats may be reduced by strict adherence to handling, sanitation, and disinfection procedures. Husbandry practices that may delay the complications of infection include regular vaccination, provision of high-quality diets, reduction of stress, control of endoparasites and ectoparasites, and early and aggressive treatment of clinical signs of disease.     

The kinetics of feline leukaemia virus shedding in experimentally infected cats are associated with infection outcome

Feline leukaemia virus (FeLV) infection in felids results mainly from oronasal exposure to infectious saliva and nasal secretions, but the potential for viral transmission through faeces and urine has not been completely characterized. In order to assess and compare potential FeLV transmission routes, we determined the viral kinetics in plasma, saliva, faeces and urine during early experimental FeLV infection (up to week 15 post-exposure) in specific pathogen-free cats. In addition to monitoring p27 antigen levels measured by ELISA, we evaluated the presence of infectious particles by cell culture assays and quantified viral RNA loads by a quantitative real-time TaqMan polymerase chain reaction. RNA load was associated with infection outcome (high load-progressive infection; low load-regressive infection) not only in plasma, but also in saliva, faeces and urine. Infectious virus was isolated from the saliva, faeces and urine of infected cats with progressive infection as early as 3-6 weeks post-infection, but usually not in cats with regressive infection. In cats with progressive infection, therefore, not only saliva but also faeces and to some extent urine might represent potential FeLV transmission routes. These results should be taken into account when modelling FeLV-host interactions and assessing FeLV transmission risk. Moreover, during early FeLV infection, detection of viral RNA in saliva may be used as an indicator of recent virus exposure, even in cats without detectable antigenaemia/viraemia. To determine the clinically relevant outcome of FeLV infection in exposed cats, however, p27 antigen levels in the peripheral blood should be measured.     

Incidence of persistent viraemia and latent feline leukaemia virus infection in cats with lymphoma

In the past, feline leukaemia virus (FeLV) infection, and also latent FeLV infection, were commonly associated with lymphoma and leukaemia. In this study, the prevalence of FeLV provirus in tumour tissue and bone marrow in FeLV antigen-negative cats with these tumours was assessed. Seventy-seven diseased cats were surveyed (61 antigen-negative, 16 antigen-positive). Blood, bone marrow, and tumour samples were investigated by two polymerase chain reaction (PCR) assays detecting deoxyribonucleic acid (DNA) sequences of the long terminal repeats (LTR) and the envelope (env) region of the FeLV genome. Immunohistochemistry (IHC) was performed in bone marrow and tumour tissue. None of the antigen-negative cats with lymphoma was detectably infected with latent FeLV. The prevalence of FeLV viraemia in cats with lymphoma was 20.8%. This suggests that causes other than FeLV play a role in tumorigenesis, and that latent FeLV infection is unlikely to be responsible for most feline lymphomas and leukaemias.     

A prospective epidemiological,clinical, and clinicopathologic study of feline leukemia virus and feline immunodeficiency virus infection in 435 cats from Greece

Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses causing significant morbidity and mortality in cats. The aim of this study was to describe the epidemiological, clinical and clinicopathologic aspects of FeLV and FIV infections in different populations of cats in Greece, including client-owned cats, stray cats and cats who live in catteries.A total of 435 cats were prospectively enrolled. Serological detection of FeLV antigen and FIV antibody was performed using a commercial in-house ELISA test kit.The results showed that 17 (3.9 %) and 40 (9.2 %) of the 435 cats were positive for FeLV antigen and FIV antibody, respectively, whereas 5 (1.1 %) had concurrent infection with FeLV and FIV. Factors that were associated with FeLV antigenemia, based on multivariate analysis, included vomiting, rhinitis, infection with FIV, neutropenia, decreased blood urea nitrogen and increased serum cholesterol and triglyceride concentrations. Factors associated with FIV seropositivity included male gender, older age, outdoor access, weight loss, fever, gingivostomatitis, skin lesions and/or pruritus and hyperglobulinemia.Various clinical signs and laboratory abnormalities were found to be significantly associated with retroviral infections, suggesting that current guidelines to test all sick cats should be followed, taking into particular consideration the high-risk groups of cats found in this study.     

Control of feline leukaemia virus

Feline leukaemia virus (FeLV) usually occurs in its natural species, the domestic cat. FeLV is also important to human individuals as a comparative model, as it may cause a variety of diseases, some malignant and some benign, such as immunosuppression, which bears a resemblance to AIDS (acquired immune deficiency syndrome) in man. FeLV is transmitted among cats by contagion. The main sources of infection are persistently infected carrier cats which continuously excrete virus. Dissemination of FeLV among cats may be prevented by identifying infected carrier cats and removing them from contact with non-infected cats. Removal programmes using indirect immunofluorescence antibody tests were applied successfully in The Netherlands. The proportion of FeLV-positive cats decreased from 9% in 1974 to approximately 3% in 1985 during such a programme. The results of a removal programme carried out in a catbreeders' society were even better: the incidence of cats positive for FeLV decreased from 11% in 1974 to less than 2% within 4 years. None of the cats tested in this society has been found to be positive for FeLV since 1984. Besides removal programmes, other methods of control, such as pre-exposure treatment, were developed to prevent the spread of FeLV. We attempted to protect kittens against oronasal infection with FeLV by treatment with virus-neutralizing (VN) monoclonal antibodies (MoAbs) directed against an epitope on the viral glycoprotein gp70. However, no protection was achieved. It is unlikely that the amount of VN antibodies, the mode and route of their application or the infectious dose of FeLV used can account for this failure. Other possible explanations for the lack of protective effect are that (i) the restricted epitope specificity of the MoAb preparation used may have led to selection of neutralization-resistant virus mutants, or (ii) other mechanisms than virus neutralization (complement-mediated lysis, antibody-dependent cell cytotoxicity), that may be involved in protection, function less efficiently with MoAb. However, in the light of our finding that an early anti-idiotypic response is observed in all cats following administration of the MoAb preparation, the rapid clearance of anti-FeLV MoAb from the circulation is a more likely explanation. Efforts were further made to develop a vaccine for controlling FeLV infection. The immunostimulating complex vaccine (FeLV-ISCOM vaccine), a subunit vaccine in which FeLV gp70 is presented in a particular manner, looks promising. The protective effect of FeLV-ISCOM vaccine was studied by vaccinating six 8-week-old SPF cats with ISCOM, followed by oronasal challenge with FeLV.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prevalence of feline immunodeficiency virus and other retroviral infections in sick cats in Italy.

Two hundred and seventy-seven sick pet cats living in Italy were tested for antibodies to feline immunodeficiency virus (FIV) and for feline leukemia virus (FeLV) antigen. Overall, 24% of the cats resulted positive for anti-FIV antibody and 18% for FeLV antigen. FIV was isolated from the peripheral mononuclear blood cells of ten out of 15 seropositive cats examined and from one out of eight saliva samples. No FIV isolations were obtained from six serum samples cultured. Feline syncytium forming virus (FeSFV) could be isolated from blood and/or saliva in ten out of 11 FIV seropositive cats examined, in six out of nine FeLV antigen positive cats, in two cats found positive for both infection markers, and in three out of 11 cats negative for both markers. Thus, the probability of isolating FeSFV was enhanced by infection with other exogenous retroviruses.     

Safety and efficacy studies of live- and killed-feline leukemia virus vaccines.

The safety and the efficacy of several feline leukemia virus (FeLV) vaccines for 16-week-old kittens were determined. Vaccines were derived from an FL74 lymphoblastoid cell line that has been in continuous tissue culture passage for about 4 years. The vaccines were made from living virus, formaldehyde-inactivated whole FL74 cells, and formaldehyde-inactivated whole virus. The efficacy of each produced vaccine was determined by challenge exposure of vaccinated cats with virulent FeLV. The two formaldehyde-inactivated vaccines were found to be safe for use in kittens. Neither vaccine produce a significant feline oncornavirus-associated cell membrane antigen or virus-neutralizing antibody response, nor did they prevent infection with virulent FeLV. The inactivated whole-virus vaccine, however, did substantially decrease the proportion of kittens infected with virulent FeLV that became persistently viremic. In contrast, the whole FL74 cell vaccine did not reduce the number of infected kittens that became persistently viremic. The live-virus vaccine was found to be both safe and efficacious. About a half of the kittens vaccinated with live virus had transient bone marrow infection that lasted from 2 to 4 weeks. Viral antigen was not detected in peripheral blood, and infective virus was not shed in saliva, urine, or feces during the period that the vaccinal virus could be recovered from the bone marrow. In addition, there was no horizontal spread of vaccinal virus from vaccinated to non-vaccinated cagemates. Within several weeks, vaccinated kittens demonstrated no clinical or hematologic abnormalities and had high serum levels of feline oncornavirus-associated cell membrane antigen and virus-neutralizing antibody. Kittens vaccinated with living FeLV were resistant to infection with virulent virus.     

A micro-enzyme-linked immunosorbent assay (ELISA) test for detection of feline leukemia virus in cats

The performance of a micro ELISA test for detection of feline leukemia virus (FeLV) infection was evaluated. The test was found specific for FeLV and feline sarcoma virus (FeSV) group-specific antigens in blood, plasma or serum of infected cats. Other common feline pathogens were negative to the test.Quantities as little as 7.8 ng of p-27 (the major group specific antigen of FeLV) per ml of sample gave positive results. The correlation between the micro ELISA test and the indirect immunofluorescent test commonly used for diagnosis of FeLV infection was 98% in 116 clinical cases and 184 samples from cats inoculated with FeLV and 100% in 100 specific pathogen-free cats.     

Seroprevalence of feline immunodeficiency virus, feline leukaemia virus and Toxoplasma gondii in stray cat colonies in northern Italy and correlation with clinical and laboratory data

Stray cat colonies in urban and rural areas of Lombardy, northern Italy, were surveyed for seroprevalence of feline immunodeficiency virus (FIV) antibodies, feline leukaemia virus (FeLV) antigen and Toxoplasma gondii IgG. Of 316 cats tested, 6.6% were positive for FIV and 3.8% were positive for FeLV infection; 203 cats were tested for T gondii IgG antibodies and a prevalence of 30.5% was detected. Statistical analysis tested the influence of provenience, age, gender, health status and laboratory results on seroprevalence and found male gender and adult age were risk factors for FIV infection. FIV-infected cats were more likely to have a decreased red blood cell count than FIV seronegative cats. No predictors were significantly associated with FeLV and T gondii seropositivity. Colony cats in this study posed a limited risk for retrovirus infection to pet cats allowed outdoors, whereas toxoplasmosis exposure was comparable with the worldwide data.