Clinical aspects of feline immunodeficiency and feline leukemia virus infection

Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses with a global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FIV can cause an acquired immunodeficiency syndrome that increases the risk of developing opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma), bone marrow suppression syndromes (mainly anemia) and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less important as a deadly infectious agent as in the last 20 years prevalence has been decreasing in most countries.     

Use of two virustatica (AZT, PMEA) in the treatment of FIV and of FeLV seropositive cats with clinical symptoms.

In the present study the therapeutic efficacy and the side effects of two antiretroviral compounds used in human acquired immunodeficiency syndrome (AIDS) research, 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine, Retrovir) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA), were investigated in the treatment of cats naturally infected with feline immunodeficiency virus (FIV) and cats naturally infected with feline leukemia virus (FeLV). AZT was administered subcutaneously at a dose of 5 mg kg-1 body weight every 12 h and PMEA was administered subcutaneously at a dose of 2.5 mg kg-1 body weight every 12 h during a 3 week hospitalization. The therapeutic efficacy of both compounds was investigated. There was a stronger potency of PMEA than of AZT on the regression of stomatitis in FIV and in FeLV infected cats. In addition, in FIV infection PMEA had a stronger effect on the improvement of the general clinical status. Both antiretroviral compounds were potent agents to improve the immunologic status of FIV infected cats by raising the CD4/CD8 ratio. In FeLV infection PMEA and AZT appeared to reduce antigenemia. The hematological side effects caused by PMEA were severe and stronger than those of AZT. Therefore the advantage of PMEA in clinical and immunologic improvement was diminished by the hematologic disorders, which do not allow long term treatment with this drug in the dose used.     

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.     

Early events in the immunopathogenesis of feline retrovirus infections.

Feline leukemia virus and feline immunodeficiency virus (FIV) are lymphotropic retroviruses that cause a wide range of diseases in domestic cats. Although it is known that both viruses are capable of infecting T lymphocytes and that infected cats are lymphopenic, it was not known how infection with either virus might alter specific lymphocyte subpopulations. Using a panel of monoclonal antibodies to feline lymphocyte subpopulations, we examined, by use of flow cytometric analysis, lymphocyte changes in cats naturally infected with FeLV or FIV and explored the early stages in the immunopathogenesis of experimentally induced infection with these viruses. Both groups of naturally infected cats had T-cell lymphopenia. In the FIV-infected cats, the T-cell decrease was principally attributable to loss of CD4+ cells, whereas CD8+ and B-cell numbers remained normal. This led to inversion of the CD4+ to CD8+ ratio in these cats. In contrast, the T-cell lymphopenia in FeLV-infected cats resulted from decrease in CD4+ and CD8+ cells, which led to a CD4+ to CD8+ ratio within normal limits. Experimentally induced infection with these 2 viruses supported these findings. Infection with FIV induced early (10 weeks after infection), chronic inversion of the CD4+ to CD8+ ratio. In contrast, infection with FeLV did not alter CD4+ to CD8+ ratio in the first 20 weeks after infection.     

Altered plasma concentrations of sex hormones in cats infected by feline immunodeficiency virus or feline leukemia virus

Gender differences may affect human immunodeficiency virus (HIV) infection in humans and may be related to fluctuations in sex hormone concentration. The different percentage of male and female cats observed to be infected by feline leukemia virus (FeLV) or feline immunodeficiency virus (FIV) has been traditionally explained through the transmission mechanisms of both viruses. However, sexual hormones may also play a role in this different distribution. To study this possibility, 17β-estradiol, progesterone, testosterone, and dehydroepiandrosterone (DHEA) concentrations were analyzed using a competitive enzyme immunoassay in the plasma of 258 cats naturally infected by FIV (FIV(+)), FeLV (FeLV(+)), or FeLV and FIV (F(-)F(+)) or negative for both viruses, including both sick and clinically healthy animals. Results indicated that the concentrations of 17β-estradiol and testosterone were significantly higher in animals infected with FIV or FeLV (P < 0.05) than in negative cats. Plasma concentrations of DHEA in cats infected by either retrovirus were lower than in negative animals (P < 0.05), and F(-)F(+) cats had significantly lower plasma values than monoinfected cats (P < 0.05). No significant differences were detected in the plasma concentration of progesterone of the four groups. No relevant differences were detected in the hormone concentrations between animal genders, except that FIV(+) females had higher DHEA concentrations than the corresponding males (P < 0.05). In addition, no differences were observed in the hormone concentrations between retrovirus-infected and noninfected animals with and without clinical signs. These results suggest that FIV and FeLV infections are associated with an important deregulation of steroids, possibly from early in the infection process, which might have decisive consequences for disease progression.     

Feline leukaemia virus (FeLV) and feline immunodeficiency virus infections in cats in the Pisa district of Tuscany, and attempts to control FeLV infection in a colony of domestic cats by vaccination

The seroprevalence of feline immunodeficiency virus (FIV) in 203 apparently healthy domestic cats living in the district of Pisa, central Italy, was 11.3 per cent, and the prevalence of feline leukaemia virus (FeLV) was 8.4 per cent. The prevalence of FIV depended significantly on the lifestyle and age of the cats; cats living outdoors were more likely to be FIV-positive than cats living indoors, and the proportion of FIV-positive cats increased with age. In contrast, there was no significant relationship between these variables and the prevalence of FeLV. There was no significant relationship between the cats' seropositivity for FIV and FeLV. The results of a five-year field study to control FeLV infection by vaccination in a colony of 30 domestic adult cats naturally exposed to the infection suggest that the vaccination was effective in FIV-negative cats, but failed to protect FIV-positive cats against FeLV.     

Long-term impact on a closed household of pet cats of natural infection with feline coronavirus, feline leukaemia virus and feline immunodeficiency virus

A closed household of 26 cats in which feline coronavirus (FCoV), feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) were endemic was observed for 10 years. Each cat was seropositive for FCoV on at least one occasion and the infection was maintained by reinfection. After 10 years, three of six surviving cats were still seropositive. Only one cat, which was also infected with FIV, developed feline infectious peritonitis (FIP). Rising anti-FCoV antibody titres did not indicate that the cat would develop FIP. The FeLV infection was self-limiting because all seven of the initially viraemic cats died within five years and the remainder were immune. However, FeLV had the greatest impact on mortality. Nine cats were initially FIV-positive and six more cats became infected during the course of the study, without evidence of having been bitten. The FIV infection did not adversely affect the cats' life expectancy.     

Prevalence of feline leukaemia virus and antibodies to feline immunodeficiency virus in cats in the United Kingdom

A representative sample of the pet cat population of the United Kingdom was surveyed. Blood samples from 1204 sick and 1007 healthy cats of known breed, age and sex were tested for antibodies to feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV). The prevalence of FIV was 19 per cent in sick cats and 6 per cent in healthy cats, and the prevalence of FeLV was 18 per cent in sick cats and 5 per cent in healthy cats; both infections were more common in domestic cats than in pedigree cats. Feline immunodeficiency virus was more prevalent in older cats but FeLV was more prevalent in younger cats. There was no difference between the prevalence of FeLV in male and female cats but male cats were more likely to be infected with FIV than female cats. No interaction was demonstrated between FIV and FeLV infections. Of the cats which were in contact with FIV in households with more than one cat, 21 per cent had seroconverted. The prevalence of FeLV viraemia in cats in contact with FeLV was 14 per cent. The clinical signs associated with FIV were pyrexia, gingivitis/stomatitis and respiratory signs, and with FeLV, pyrexia and anaemia. It was concluded that both viruses were significant causes of disease, and that the cats most likely to be infected with FIV were older, free-roaming male cats and for FeLV, younger, free-roaming cats.     

Tumor necrosis factor alpha levels in cats experimentally infected with feline immunodeficiency virus: effects of immunization and feline leukemia virus infection.

Tumor necrosis factor alpha (TNF alpha) levels were determined by enzyme-linked immunosorbent assay (ELISA) and by cell culture bioassay in supernatants of lipopolysaccharide-stimulated feline monocyte cultures and in cat serum samples. There was a good correlation between the results obtained by the two methods. From the fact that TNF alpha was neutralized quantitatively by antibodies to human TNF alpha in feline monocyte supernatants and in feline sera, it was concluded that feline TNF alpha immunologically cross-reacts with human TNF alpha and that the human TNF alpha ELISA can be used to quantitate feline TNF alpha. During the first 6 months after experimental feline immunodeficiency virus (FIV) infection no differences in serum TNF alpha values were observed between infected and non-infected cats. TNF alpha levels increased significantly after primary vaccination with a feline leukemia virus (FeLV) vaccine in FIV infected cats over those in the non-infected controls. During secondary immune response TNF alpha levels rose transiently for a period of a few days in both the FIV positive and the FIV negative cats. After FeLV challenge, TNF alpha levels increased in all animals challenged with virulent FeLV for a period of 3 weeks. This period corresponded to the time necessary to develop persistent FeLV viremia in the control cats. It was concluded from these experiments that in the asymptomatic phase of FIV infection no increased levels of TNF alpha are present, similar to the situation in asymptomatic HIV infected humans. Activation of monocytes/macrophages in FIV infected cats by stimuli such as vaccination or FeLV challenge readily leads to increased levels of TNF alpha.     

2008 American Association of Feline Practitioners' feline retrovirus management guidelines

Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are among the most common infectious diseases of cats. Although vaccines are available for both viruses, identification and segregation of infected cats form the cornerstone for preventing new infections. Guidelines in this report have been developed for diagnosis, prevention, treatment, and management of FeLV and FIV infections. All cats should be tested for FeLV and FIV infections at appropriate intervals based on individual risk assessments. This includes testing at the time of acquisition, following exposure to an infected cat or a cat of unknown infection status, prior to vaccination against FeLV or FIV, prior to entering group housing, and when cats become sick. No test is 100% accurate at all times under all conditions; results should be interpreted along with the patient's health and risk factors. Retroviral tests can diagnose only infection, not clinical disease, and cats infected with FeLV or FIV may live for many years. A decision for euthanasia should never be based solely on whether or not the cat is infected. Vaccination against FeLV is highly recommended in kittens. In adult cats, antiretroviral vaccines are considered non-core and should be administered only if a risk assessment indicates they are appropriate. Few large controlled studies have been performed using antiviral or immunomodulating drugs for the treatment of naturally infected cats. More research is needed to identify best practices to improve long-term outcomes following retroviral infections in cats.     

Chronic oral infections of cats and their relationship to persistent oral carriage of feline calici-, immunodeficiency, or leukemia viruses.

Two hundred and twenty-six cats from the Veterinary Medical Teaching Hospital (VMTH), a cat shelter, and a purebred cattery were tested for chronic feline calicivirus (FCV), feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) infections. Chronic oral carriage of FCV was present in about one-fifth of the cats in each of the groups. FIV infection was not present in the purebred cattery, was moderately prevalent (8%) in the pet population of cats examined at the VMTH for various complaints and was rampant in the cat shelter (21%). Unexpectedly high FeLV infection rates were found in the hospital cat population (28%) and in the purebred cattery (36%), but not in the cat shelter (1.4%). FCV and FeLV infections tended to occur early in life, whereas FIV infections tended to occur in older animals. From 43 to 100% of the cats in these environments had oral cavity disease ranging from mild gingivitis (23-46%), proliferative gingivitis (18-20%), periodontitis (3-32%) and periodontitis with involvement of extra-gingival tissues (7-27%). Cats infected solely with FCV did not have a greater likelihood of oral lesions, or more severe oral disease, than cats that were totally virus free. This was also true for cats infected solely with FeLV, or for cats dually infected with FeLV and FCV. Cats infected solely with FIV appeared to have a greater prevalence of oral cavity infections and their oral cavity disease tended to be more severe than cats without FIV infection. FIV-infected cats that were coinfected with either FCV, or with FCV and FeLV, had the highest prevalence of oral cavity infections and the most severe oral lesions.     

Vaccination of cats experimentally infected with feline immunodeficiency virus, using a recombinant feline leukemia virus vaccine.

A group of 15 cats experimentally infected with a Swiss isolate of feline immunodeficiency virus (FIV) and a group of 15 FIV-negative control cats were inoculated with an FeLV vaccine containing recombinant FeLV-envelope. High ELISA antibody titer developed after vaccination in FIV-positive and FIV-negative cats. Vaccinated and nonvaccinated controls were later challenge exposed by intraperitoneal administration of virulent FeLV subtype A (Glasgow). Although 12 of 12 nonvaccinated controls became infected with FeLV (10 persistently, 2 transiently), only 1 of 18 vaccinated (9 FIV positive, 9 FIV negative) cats had persistent and 2 of 18 had transient viremia. From these data and other observations, 2 conclusions were drawn: In the early phase of FIV infection, the immune system is not depressed appreciably, and therefore, cats may be successfully immunized; a recombinant FeLV vaccine was efficacious in protecting cats against intraperitoneal challenge exposure with FeLV.     

Serological survey of Toxoplasma gondii,feline immunodeficiency virus and feline leukaemia virus in urban stray cats in Belgium

Three hundred and forty-six serum samples taken between 1998 and 2000 from urban stray cats in the city of Ghent were tested for antibodies to Toxoplasma gondii and feline immunodeficiency virus (FIV), and antigens of feline leukemia virus (FeLV). Of these 346 samples, 243 (70.2 per cent) were seropositive for Tgondii. Thirty-nine cats (11.3 per cent) had antibodies against FIV and 13 (3.8 per cent) had circulating antigens of FeLV. Fewer of the female cats had FIV and heavier cats had a higher seroprevalence of FIV. Exact logistic regression showed that cats that were infected with FIV were more likely to be infected with T gondii (P = 0.04), and the cats with FIV had a higher titre of Tgondii antibodies than FIV-negative animals. However, FeLV was not associated with either T gondii or FIV.     

Seroprevalence of feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) in shelter cats on the island of Newfoundland,Canada

Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are retroviruses found within domestic and wild cat populations. These viruses cause severe illnesses that eventually lead to death. Housing cats communally for long periods of time makes shelters at high risk for virus transmission among cats. We tested 548 cats from 5 different sites across the island of Newfoundland for FIV and FeLV. The overall seroprevalence was 2.2% and 6.2% for FIV and FeLV, respectively. Two sites had significantly higher seroprevalence of FeLV infection than the other 3 sites. Analysis of sequences from the FeLV env gene (envelope gene) from 6 positive cats showed that 4 fell within the FeLV subtype-A, while 2 sequences were most closely related to FeLV subtype-B and endogenous feline leukemia virus (en FeLV). Varying seroprevalence and the variation in sequences at different sites demonstrate that some shelters are at greater risk of FeLV infections and recombination can occur at sites of high seroprevalence.     

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.     

Suppression of feline bone marrow fibroblast colony-forming units by feline leukemia virus

Bone marrow fibroblast colony-forming units (CFU-F) were evaluated in cats experimentally infected with feline leukemia virus (FeLV). Cats that developed persistent viral infection and anemia (progressor cats) had a progressive decrease in the number of CFU-F at 2, 4, 6, 8, and 10 weeks after inoculation with FeLV. This suppression of CFU-F number in progressor cats ranged from 16 to 44% of the preinoculation CFU-F value. Cats that did not develop persistent viral infection or anemia (regressor cats) had decreased numbers of CFU-F (24% of the preinoculation CFU-F value) at 2 weeks after inoculation, but normal CFU-F numbers at 4, 6, 8, and 10 weeks after inoculation. In vitro incubation of bone marrow mononuclear cells from healthy cats with the 15,000-dalton envelope protein of FeLV resulted in decreased number of CFU-F (21% of that of untreated cultures). The number of CFU-F from bone marrow mononuclear cells incubated with the 27,000-dalton core protein of FeLV was similar to that from untreated cultures.     

Feline immunodeficiency virus, feline leukemia virus and Toxoplasma gondii in stray and household cats in Kerman-Iran: Seroprevalence and correlation with clinical and laboratory findings

This study was carried out to determine the seroprevalence of feline leukemia virus (FeLV), feline immunodeficiency virus (FIV) and Toxoplasma gondii (T. gondii) infection among stray and owned cats in southeastern Iran and to identify the influence of age, sex, lifestyle, health status, and laboratory findings on seropositivity. The overall infection rate for FIV, FeLV, and T. gondii was 19.2%, 14.2%, and 32.1% respectively. Results of the multivariate logistic regression analysis showed that old adults more likely to be seropositive than juveniles for FIV, FeLV, and T. gondii (adjusted odds ratios [ORs], 1.84, 1.56, and 2.57 respectively). Anemic and diseased cats ([ORs], 6.62 and 0.9) were at a greater risk of testing positive for FeLV. Male cats were 4.91 times as likely to have FIV as were female and hyperglobulinemia was significantly more prevalent in FIV-infected cats ([ORs], 3.4). In conclusion, FIV and FeLV seem to be endemic in Iran and retroviral-associated immunosuppression may be a risk factor for active toxoplasmosis in infected cats.     

Epidemiologic and clinical aspects of feline immunodeficiency virus infection in cats from the continental United States and Canada and possible mode of transmission

The epidemiologic features of feline immunodeficiency virus (FIV) infection were evaluated in 2,765 cats from the United States and Canada. Of these cats, 2,254 were considered by veterinarians to be at high risk for the infection, and 511 were healthy cats considered to be at low or unknown risk. Of the cats in the high-risk group, 318 (14%) were found to be infected with FIV. The infection rate among low- or unknown-risk cats was 6 of 511 (1.2%). Male cats in the high-risk group were 3 times more likely to be infected than were females, similarly as were cats greater than 6 years old, compared with younger cats; domestic cats, compared with purebred cats; and free-roaming cats, compared with confined cats. Feline immunodeficiency virus and FeLV infections did not appear to be linked with each other; 16% of FeLV-infected cats in the high- and low-risk groups were coinfected with FIV. In contrast, there was a pronounced linkage between FIV and feline syncytium-forming virus (FeSFV) infections. Seventy-four percent of FeSFV-infected cats in the high-risk study group were coinfected with FIV, compared with a 38% FIV infection rate among cats that were not infected with FeSFV. The major clinical manifestations associated with FIV infection in cats that were surveyed included chronic oral cavity infections (56%), chronic upper respiratory tract disease (34%), chronic enteritis (19%), and chronic conjunctivitis (11%). Bacterial infections of the urinary tract (cystitis), skin, and ears were seen in a small proportion of cats.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.