Adaptation of feline immunodeficiency virus subtype B strain TM2 to a feline astrocyte cell line (G355-5 cells)

Based on receptor usage during infection, feline immunodeficiency virus (FIV) isolates can be divided into two groups; those that require feline CD134 (fCD134) as a primary receptor in addition to CXCR4 to enter the cells, and those that require CXCR4 only. Most primary isolates, including strain TM2, belong to the former group and cannot infect a feline astrocyte cell line (G355-5 cells) due to a lack of fCD134 expression. In a previous study, we found that G355-5 cells transduced with fCD134 (termed G355-5/fOX40 cells) were susceptible to strain TM2 and the inoculated cells became persistently infected. In this study, we examined the phenotype of the virus prepared from the persistently infected cells (termed strain TM2PI). Intriguingly, strain TM2PI replicated well in na?ve G355-5 cells and the inoculated G355-5 cells (termed G355-5/TM2PI cells) became persistently infected. The infection of TM2PI in G355-5 cells was inhibited by CXCR4 antagonist AMD3100 and TM2PI infected other fCD134-negative, CXCR4-positive cell lines, FeTJ and 3201 cells. Four amino acid substitutions were found in the Env protein of the strain TM2PI when compared with that of the parental strain TM2. Among the substitutions, the Env amino acid position at 407 of TM2PI was substituted to lysine which has been known to be responsible for the FIV tropism for Crandell feline kidney cells. The strain TM2PI will be useful for studying the receptor switching mechanism and FIV pathogenesis in cats.     

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.     

Epizootiologic association between feline immunodeficiency virus infection and feline leukemia virus seropositivity

Five hundred twenty-one feline serum samples submitted to the Texas Veterinary Medical Diagnostic Laboratory between Nov 1, 1988, and Jan 31, 1989 were tested for antibody to feline immunodeficiency virus (FIV) by use of an ELISA. The prevalence of FIV infection in this population was 11.3% (95% confidence interval: 8.6 to 14.0%). Serologic test results for FeLV were available for 156 of the 521 cats. A significant (P = 0.008) association between FIV infection and FeLV seropositivity was observed; FeLV-positive cats were nearly 4 times more likely to be seropositive for FIV than were FeLV-negative cats. The association remained statistically significant (P = 0.021) after adjusting for age and gender, using multiple-logistic regression analysis.     

Pathogenesis of a Texas feline immunodeficiency virus isolate: an emerging subtype of clade B

We have recently provided evidence that Texas feline immunodeficiency virus (FIV-TX) isolates are an emerging subtype sharing a common ancestry with clade B isolates. Specific, pathogen-free cats were infected, intravenously, with 500, 2000 or 8000TCID(50) of the FIV-TX53 virus to study the acute stage of infection. Infection of cats resulted in lymphadenopathy at 10 days post-infection (p.i.). By 7 weeks p.i., gag specific antibody could be detected from sera of all infected cats. Virus could be detected by culturing PBMC and by nested capsid PCR. A reduction in the absolute numbers of lymphocytes and neutrophils was observed in infected cats although there was no trend identified between this reduction and the viral dose administered. By 11 weeks p.i., the CD4(+)/CD8(+) T cell ratios from all infected cats had dropped from approximately 2 to below 1. While decrease in the ratio was dependent on the viral dose, the T cell ratios of cats receiving the highest dose had significantly dropped below 1 by 4-7 weeks p.i. This decrease in the ratio was accompanied by a sharp and temporal decline in the absolute CD4(+) T cells and a slight increase in the absolute CD8(+) T cell numbers with a dramatic expansion of cells with CD8beta(low) chain expression.     

Quality of different in-clinic test systems for feline immunodeficiency virus and feline leukaemia virus infection

Many new diagnostic in-house tests for identification of feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) infection have been licensed for use in veterinary practice, and the question of the relative merits of these kits has prompted comparative studies. This study was designed to define the strengths and weaknesses of seven FIV and eight FeLV tests that are commercially available. In this study, 536 serum samples from randomly selected cats were tested. Those samples reacting FIV-positive in at least one of the tests were confirmed by Western blot, and those reacting FeLV-positive were confirmed by virus isolation. In addition, a random selection of samples testing negative in all test systems was re-tested by Western blot (100 samples) and by virus isolation (81 samples). Specificity, sensitivity, positive and negative predictive values of each test and the quality of the results were compared.     

Prevalence of feline leukemia virus infection and serum antibodies against feline immunodeficiency virus in unowned free-roaming cats

OBJECTIVE: To determine prevalence of FeLV infection and serum antibodies against feline immunodeficiency virus (FIV) in unowned free-roaming cats. DESIGN: Cross-sectional serologic survey. ANIMALS: 733 unowned free-roaming cats in Raleigh, NC, and 1,143 unowned free-roaming cats in Gainesville, Fla. RESULTS: In Raleigh, overall prevalence of FeLV infection was 5.3%, and overall seroprevalence for FIV was 2.3%. In Gainesville, overall prevalence of FeLV infection was 3.7%, and overall seroprevalence for FIV was 4.3%. Overall, FeLV prevalence was 4.3%, and seroprevalence for FIV was 3.5%. Prevalence of FeLV infection was not significantly different between males (4.9%) and females (3.8%), although seroprevalence for FIV was significantly higher in male cats (6.3%) than in female cats (1.5%). CONCLUSIONS AND CLINICAL RELEVANCE: Prevalence of FeLV infection and seroprevalence for FIV in unowned free-roaming cats in Raleigh and Gainesville are similar to prevalence rates reported for owned cats in the United States. Male cats are at increased risk for exposure to FIV, compared with female cats.     

The prevalence of feline immunodeficiency virus infection in hyperthyroid cats

One hundred and thirty-four male and female hyperthyroid cats (mean age 11.9 years) were tested for the presence of feline immunodeficiency virus antibodies. Thirty-two (23.9%) were positive. The prevalence of feline immunodeficiency virus antibodies was greater in male cats (30.5%) than in female cats (17.2%). The prevalence of feline immunodeficiency virus infection in hyperthyroid cats is similar to the prevalence of feline immunodeficiency virus in the sick cat population and less than that of sick aged cats at the Massey University Clinic and Hospital. The findings of this survey do not support involvement of feline immunodeficiency virus in the pathogenesis of hyperthyroidism in the cat.     

Clinical and pathological findings in feline immunodeficiency virus experimental infection.

A study is described of the clinical and pathological findings in 20 specific pathogen free cats infected when 1 year old with feline immunodeficiency virus and monitored over 12 months. Cats were divided into two groups (A and B). The clinical and clinicopathological features were studied in Group A. In Group B, at 1, 2, 4, 9 and 12 months post infection two cats were necropsied. Clinically all cats developed generalised lymphadenopathy, six cats were neutropenic and five cats lymphopenic. Three cats became febrile with conjunctivitis and anterior uveitis and one of these cats ultimately developed jaundice. Postmortem examinations confirmed a generalised lymphadenopathy involving peripheral and visceral lymph nodes with concurrent stimulation of splenic white matter and mucosal lymphoid tissue of the digestive tract and conjunctiva. Within the lymph nodes there was a reactive follicular hyperplasia accompanied by a paracortical hyperplasia with an increased paracortical vascularity. Unusual features were the presence of lymphoid follicles in the bone marrow, thymus and parathyroid tissue. In addition, aggregates of lymphoid cells were found within salivary glands, kidneys, sclera and choroid of the eye. One cat developed a lymphosarcoma affecting the liver and kidneys at 36 weeks post infection. The cat with jaundice had a cholangitis with marked biliary epithelial hyperplasia.     

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.     

Seroepidemiological and clinical survey of feline immunodeficiency virus infection in northern Italy

Four hundred and thirty-nine feline serum samples from cats with different living conditions in the north of Italy were tested for antibodies to feline immunodeficiency virus (FIV) and for antigen of Feline Leukemia Virus by enzyme-linked immunosorbent assay. A Western blot technique was also used on the positive sera in order to confirm the presence of specific antibodies to FIV. The Western blot enabled the detection of a false positive serum. The prevalence of FIV infection in this population was 12.5% and among the seropositive cats a greater proportion was male (74.5%) than female (25.5%). A correlation between the clinical status and the evolution of the pathology is described together with a score based on the severity of the stomatitis in infected cats. The Western blot patterns of positive samples were then compared with the stage of the pathology. Statistical analysis on the distribution of FIV in stray cats, cats with garden and courtyard access and strictly house-confined cats showed a highly significant risk of the infection in the first group.     

Lymphosarcoma in experimentally induced feline immunodeficiency virus infection [corrected]

A cat experimentally infected with feline immunodeficiency virus (FIV) but known to be free of feline leukaemia virus (FeLV) developed lymphosarcoma. The lesions in the liver and kidneys were present nine months after infection, when the cat was 21 months old. The cat had no overt signs of immunodeficiency and it is suggested that the B cell activation induced shortly after FIV infection produced a large pool of proliferating lymphocytes from which the malignant cells emerged.     

Seroprevalence of feline leukemia virus and feline immunodeficiency virus infection among cats in North America and risk factors for seropositivity

OBJECTIVE: To determine seroprevalence of FeLV and FIV infection among cats in North America and risk factors for seropositivity. DESIGN: Prospective cross-sectional survey. ANIMALS: 18,038 cats tested at 345 veterinary clinics (n=9,970) and 145 animal shelters (8,068) between August and November 2004. PROCEDURE: Cats were tested with a point-of-care ELISA for FeLV antigen and FIV antibody. A multivariable random effects logistic regression model was used to identify risk factors significantly associated with seropositivity while accounting for clinic-to-clinic (or shelter) variability. RESULTS: 409 (2.3%) cats were seropositive for FeLV antigen, and 446 (2.5%) cats were seropositive for FIV antibody; 58 (0.3%) cats were seropositive for infection with both viruses. Multivariable analysis indicated that age, sex, health status, and cat lifestyle and source were significantly associated with risk of seropositivity, with adults more likely to be seropositive than juveniles (adjusted odds ratios [ORs], 2.5 and 2.05 for FeLV and FIV seropositivity, respectively), sexually intact adult males more likely to be seropositive than sexually intact adult females (adjusted ORs, 2.4 and 4.66), and outdoor cats that were sick at the time of testing more likely to be seropositive than healthy indoor cats (adjusted ORs, 8.89 and 11.3). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that certain characteristics, such as age, sex, health status, and lifestyle, are associated with risk of FeLV and FIV seropositivity among cats in North America. However, cats in all categories were found to be at risk for infection, and current guidelines to test all cats at the time of acquisition and again during illness should be followed.     

Chemokine receptors and co-stimulatory molecules: unravelling feline immunodeficiency virus infection

Feline immunodeficiency virus (FIV) infection of the domestic cat induces an immunodeficiency characterised by a gradual depletion of CD4+ T-helper lymphocytes. The virus targets T-helper cells by way of an interaction between its envelope glycoprotein (Env) and the cell surface molecule CD134 (OX40), a member of the nerve growth factor receptor/tumour necrosis factor receptor superfamily. The Env–CD134 interaction is a necessary prerequisite for the subsequent interaction with CXCR4, the only chemokine receptor identified to date to act as a co-receptor for FIV. As T-helper cell expression of CD134 and CXCR4 is restricted to activated cells, FIV targets selectively antigen-specific T-helper cells. With disease progression the cell tropism of the virus expands; this may be the result of changes in the way in which Env interacts with CD134, a less stringent Env–CD134 interaction enabling the Env to interact more readily with CXCR4 and thus broadening the cell tropism of virus. In contrast, viruses that are present in early infection may have a narrower cell tropism, reflecting a more stringent interaction with CD134. Accordingly, “early” viruses may target CD134-expressing cells more efficiently and be more resistant to neutralising antibody. It is these early viruses that may be transmitted and should be considered as candidates for the development of vaccine regimes and novel therapeutic agents.