Interaction of acute feline herpesvirus-1 and chronic feline immunodeficiency virus infections in experimentally infected specific pathogen free cats.

Cats with or without chronic feline immunodeficiency virus (FIV) infection were exposed to feline herpesvirus, type 1 (FHV-1). FIV infected cats became sicker than non-FIV infected cats and required more supportive treatment. However, there were no differences in the length of their illness or in the levels and duration of FHV-1 shedding. FHV-1 infection caused a transient neutrophilia at Day 7 with a rapid return to preinfection levels. The neutrophilia coincided with a transient lymphopenia that was accompanied by a decline in both CD4+ and CD8+ T-lymphocytes. A brief decrease in the CD4+/CD8+ T-lymphocyte ratio occurred at Day 14 in both FIV infected and non-infected cats. This decrease was mainly the result of an absolute and transient increase in CD8+ T-lymphocytes. CD4+ and CD8+ T-lymphocyte numbers and CD4+/CD8+ T-lymphocyte ratios returned to baseline within 4-8 weeks in both FIV infected and non-infected cats. FIV infected cats produced less FHV-1 neutralizing antibodies during the first 3 weeks of infection than non-FIV infected animals. The IgM FHV-1 antibody response was depressed in FIV infected cats whereas the IgG antibody response was unaffected. FHV-1 infection evoked a comparable transient loss of lymphocyte blastogenic responses to concanavalin A and pokeweed mitogen in both FIV infected and non-infected cats. However, response to pokeweed mitogen took longer to return to normal in FIV infected animals. Lymphocytes from FIV infected cats had a greater and more sustained proliferative response to FHV-1 antigen than non-FIV infected cats. The ongoing IgG antibody response to FIV was not affected by FHV-1 infection.     

The use of human hematopoietic growth factors (rhGM-CSF and rhEPO) as a supportive therapy for FIV-infected cats

Recombinant human GM-CSF (rhGM-CSF) and erythropoietin (rhEPO) were tested on chronically FIV-infected laboratory cats and uninfected specific-pathogen-free (SPF) cats. In Study 1, a total of eight cats (four cats per group of either infected or uninfected cats) received subcutaneous injection (twice a day) for 2 weeks with 5 microg/kg of rhGM-CSF, while seven cats (three SPF and four FIV-infected cats) served as the placebo-treated control cats. Four of eight rhGM-CSF-treated cats (two cats each from infected and uninfected groups) developed elevated WBC counts which peaked at Days 5-8 of treatment when compared to placebo-treated cats. The elevated WBC counts were attributed to the increase in either neutrophils, lymphocytes, eosinophils, monocytes, or their combinations. The RBC counts, platelet counts, and blood chemistry were not significantly affected by the treatment. Anti-rhGM-CSF antibodies were detected in six of eight rhGM-CSF-treated cats by Day 35 post-first treatment. All rhGM-CSF-treated infected cats but no placebo-treated infected cats had 1-2 log increase in FIV load in the PBMC during the treatment. In vitro studies suggest that rhGM-CSF has an effect on FIV replication in T cells but not in alveolar macrophages. Five of eight rhGM-CSF-treated cats had low-grade fever at 3-6 days of treatment. In Study 2, four cats per group of either infected or uninfected cats were treated (subcutaneously once a day) three times a week for 2 weeks with 100U/kg of rhEPO and monitored as before, while seven cats (three SPF and four FIV-infected cats) served as the placebo-treated control cats. All rhEPO-treated cats had a gradual increase in RBC, Hgb, and PCV counts which peaked at 2-4 weeks post-first rhEPO treatment, whereas none of the placebo-treated cats had significant increase in these parameters. The rhEPO-treated cats also developed elevated WBC counts consisting of either elevated neutrophils, lymphocytes, or their combination by 4 weeks post-first treatment but there was no statistical difference between rhEPO-treated and placebo-treated groups. None of the cats developed anti-rhEPO antibodies and no remarkable changes in blood chemistry, clinical signs, and FIV loads or FIV antibody titers were observed. Overall, rhEPO can be used safely on FIV-infected cats but the use of rhGM-CSF on FIV-infected cats should be performed with discretion.     

Immunization-induced decrease of the CD4+:CD8+ ratio in cats experimentally infected with feline immunodeficiency virus.

In a previous experiment a group of 15 specified pathogen free (SPF) cats were experimentally infected with a Swiss isolate of feline immunodeficiency virus (FIV). A group of 15 SPF cats served as FIV negative controls. Nine cats of each group were vaccinated with a recombinant feline leukemia virus (FeLV) vaccine, six cats in each group with a placebo vaccine. All vaccinated cats developed high antibody titers to FeLV and were protected against subsequent FeLV challenge infection. In both control groups five of six cats became persistently infected with FeLV. Unexpectedly, the primary immune response to the vaccine antigen was significantly higher in the FIV positive group than in the FIV negative. The secondary response was stronger in the FIV negative cats. The goal of the present investigation was to further study the immune response in these 30 cats. They were immunized twice with the synthetic peptide L-tyrosine-L-glutamic acid-poly(DL-alanine)-poly(L-lysine) (TGAL) 21 days apart. Blood samples were collected on four occasions during the immunization process. They were tested for antibodies to TGAL, complete blood cell counts and CD4+, CD8+ and pan-T-lymphocyte counts. The following observations were made: (1) in contrast to the FeLV vaccine experiment, the primary immune response to TGAL was not significantly stronger in the FIV positive cats when tested by enzyme-linked immunosorbent assay (2). The absolute size of the CD4+ lymphocyte population was distinctly smaller in the FIV positive than in the FIV negative cats. The lowest CD4+ values were found in the dually FIV/FeLV infected cats. (3) A population of CD8+ lymphocytes was identified that was characterized by a distinctly weaker fluorescence. The size of this population increased in FIV positive and decreased in FIV negative cats during the TGAL immunization experiment. (4) The CD4+:CD8+ ratio increased in FIV negative cats during TGAL immunization from 1.9 to 2.3. In contrast, in FIV positive animals the CD4+:CD8+ ratio decreased significantly from 1.9 to 1.3 during the same period. From these and earlier data it was concluded that in short-term FIV infection the immune response to T-cell dependent antigens may be increased over that of the controls. Immune suppression develops gradually with duration of the infection. The significant drop of the CD4+:CD8+ ratio over a 5 week immunization period suggests that antigenic stimulation may accelerate the development of immune suppression in FIV positive cats. If this is a general feature, FIV infection may provide a particularly interesting model for studying the pathogenesis of AIDS.     

Differentiation of feline immunodeficiency virus vaccination, infection, or vaccination and infection in cats

BACKGROUND: Serodiagnosis of feline immunodeficiency virus (FIV) is complicated by the use of a formalin-inactivated whole-virus FIV vaccine. Cats respond to immunization with antibodies indistinguishable from those produced during natural infection by currently available diagnostic tests, which are unable to distinguish cats that are vaccinated against FIV, infected with FIV, or both. HYPOTHESIS: An enzyme-linked immunosorbent assay (ELISA) detecting antibodies against formalin-treated FIV whole virus and untreated transmembrane peptide will distinguish uninfected from infected cats, regardless of vaccination status. ANIMALS: Blood samples were evaluated from uninfected unvaccinated cats (n = 73 samples), uninfected FIV-vaccinated cats (n = 89), and FIV-infected cats (n = 102, including 3 from cats that were also vaccinated). METHODS: The true status of each sample was determined by virus isolation. Plasma samples were tested for FIV antibodies by a commercial FIV diagnostic assay and an experimental discriminant ELISA. RESULTS: All samples from uninfected cats were correctly identified by the discriminant ELISA (specificity 100%). Of the samples collected from FIV-infected cats, 99 were correctly identified as FIV-infected (sensitivity 97.1%). CONCLUSIONS AND CLINICAL IMPORTANCE: With the exception of viral isolation, the discriminant ELISA is the most reliable assay for diagnosis of FIV. A practical strategy for the diagnosis of FIV infection would be to use existing commercial FIV antibody assays as screening tests. Negative results with commercial assays are highly reliable predictors for lack of infection. Positive results can be confirmed with the discriminant ELISA. If the discriminant ELISA is negative, the cat is probably vaccinated against FIV but not infected. Positive results are likely to represent infection.     

Altered surface antigen expression on peripheral blood mononuclear cells in cats infected with feline immunodeficiency virus.

Expression of CD4, CD8, IL-2 receptor alpha chain (IL-2R alpha), and MHC class II (MHC-II) on peripheral blood mononuclear cells were examined in cats infected with feline immunodeficiency virus (FIV). CD4/CD8 T cell ratio in FIV-infected cats was slightly decreased, as compared with that in specific-pathogen-free (SPF) cats. However, there was no statistical differences between them. The number of circulating IL-2R alpha+ cells in FIV-infected cats was higher than that in healthy cats, whereas induction of IL-2R alpha expression by concanavalin A (Con A) stimulation was depressed in FIV-infected cats. By using two-color cytofluorometry, Con A-induced enhancement of IL-2R alpha expression was found to be reduced in both CD4+ and CD8+ populations in PBMC from FIV-infected cats. The circulating MHC-II+ cells were also increased in FIV-infected cats. Furthermore, the induction of IL-2R alpha expression on PBMC after Con A-stimulation significantly depressed by FIV inoculation in vitro. These results suggest that FIV activates PBMC in vivo via direct and/or indirect mechanisms, leading to the unresponsive state of T cells to further stimuli in vitro.     

Mutations in feline immunodeficiency (FIV) virus envelope gene V3-V5 regions in FIV-infected cats

The envelope (Env) gene V3-V5 regions of the feline immunodeficiency virus (FIV) encode the neutralizing epitopes. Since mutations in these regions induce resistance to viral neutralizing antibodies, they may influence the effects of vaccines. To examine the in vivo mutation rate in these regions, we cloned cDNA for the Env gene V3-V5 regions from the PBMC of experimentally FIV-infected cats, and compared the deduced amino acid sequences. Blood or plasma from an FIV Shizuoka strain-infected cat was inoculated into a second group of SPF cats, and their blood or plasma was inoculated into the third group. The amino acid sequence encoded by the viral gene of the first cat was compared with those encoded by the viral genes of a total of eight cats in the second and third groups (two and six cats, respectively). The amino acid sequences in two cats in the second and third groups were 100% homologous and in one cat in the third group was 98.3% homologous to that in the first infected cat. Five cats had the same sequence, which was 97.8% homologous to that in the first infected cat. Three kittens, born 2 months after the inoculation of the FIV Aomori-2 strain into the mother cat, were anti-FIV negative at 4 weeks after birth, but became seropositive at 33 weeks after birth, confirming FIV infection. Comparison of the encoded amino acid sequences of the viral gene in two cats at 48 weeks after birth showed 100% homology to that of the virus inoculated into the mother cat, and the remaining one cat had a single residue substitution, resulting in 99.4% homology. These results suggest that the FIV Env gene V3-V5 regions are stably maintained for at least 1-2 years after infection.     

Loss of naïve (CD45RA+) CD4+ lymphocytes during pediatric infection with feline immunodeficiency virus

Feline immunodeficiency virus (FIV) infection of cats is an animal model for the pathogenesis of CD4+ lymphopenia and thymus dysfunction in HIV-infected humans. Recently, a monoclonal antibody (755) was reported to recognize the feline homologue to CD45RA, allowing the enumeration of na?ve T cells in cats. We tested the hypothesis that pediatric FIV infection would be associated with a selective loss of na?ve CD4+ lymphocytes by inoculating newborn cats with a pathogenic clone of FIV (JSY3) or a related clone with an inactive ORF-A gene (JSY3-DeltaORFA), and compared the data to age-matched uninfected control cats. Both FIV inocula were associated with a reduction in the CD4-CD8 ratio (p=0.01), which was attributable to a disproportionate loss of na?ve CD4+ cells (p=0.01) vs. na?ve CD8+ cells. Therefore, the reduced CD4:CD8 ratio in FIV-infected juvenile cats is associated with a selective depletion of na?ve CD4+ cells from the blood.     

Quantification of viral ribonucleic acid in plasma of cats naturally infected with feline immunodeficiency virus

OBJECTIVE: To assess plasma viral RNA concentration in cats naturally infected with feline immunodeficiency virus (FIV). ANIMALS: 28 FIV-infected cats. PROCEDURE: Cats were categorized into 1 of the 3 following stages on the basis of clinical signs: asymptomatic (nonclinical) carrier (AC; n = 11), acquired immunodeficiency syndrome-related complex (ARC; 9), or acquired immunodeficiency syndrome (AIDS; 8). Concentration of viral RNA in plasma (copies per ml) was determined by use of a quantitative competitive polymerase chain reaction (QC-PCR) assay. Total lymphocyte count, CD4+ cell and CD8+ cell counts, and the CD4+ cell count-to-CD8+ cell count ratio were determined by use of flow cytometry. RESULTS: Plasma viral RNA concentration was significantly higher in cats in the AIDS stage, compared with cats in AC and ARC stages. Most (5/7) cats in the AIDS stage had low total lymphocyte, CD4+ cell, and CD8+ cell counts. CONCLUSIONS AND CLINICAL RELEVANCE: Concentration of plasma viral RNA is a good indicator of disease progression in FIV-infected cats, particularly as cats progress from the ARC to the AIDS stage. Determination of CD4+ and CD8+ cell counts can be used as supportive indicators of disease progression.     

Effects of an oral superoxide dismutase enzyme supplementation on indices of oxidative stress, proviral load, and CD4:CD8 ratios in asymptomatic FIV-infected cats

This study was designed to test the effect of antioxidant supplementation on feline immunodeficiency virus (FIV)-infected felines. Six acutely FIV-infected cats (> or =16 weeks post-inoculation) were given a propriety oral superoxide dismutase (SOD) supplement (Oxstrin; Nutramax Laboratories) for 30 days. Following supplementation, the erythrocyte SOD enzyme concentration was significantly greater in the supplemented FIV-infected group than the uninfected control group or the unsupplemented FIV-infected group. The CD4+ to CD8+ ratio increased significantly (0.66-0.88) in the SOD supplemented FIV-infected cats but not in the unsupplemented FIV-infected cats. Proviral load and reduced glutathione (GSH) levels in leukocyte cell types did not change significantly following supplementation. Antioxidant supplementation resulted in an increase in SOD levels, confirming the oral bioavailability of the compound in FIV-infected cats. This result warrants further investigation with trials of antioxidant therapy in FIV-infected cats that are showing clinical manifestations of their disease, as well as in other feline patients where oxidative stress likely contributes to disease pathogenesis, such as diabetes mellitus and chronic renal failure.     

16alpha-Bromo-epiandrosterone therapy modulates experimental feline immunodeficiency virus viremia: initial enhancement leading to long-term suppression

16alpha-Bromo-epiandrosterone (epiBr), a synthetic derivative of the natural hormone dehyroepiandrosterone (DHEA), was evaluated for its effects on feline immunodeficiency virus (FIV) infection in experimental cats. The rationale for this study was based on the ability of DHEA to significantly reduce the mortality to viral infections in mice. DHEA and epiBr also have demonstrable in vitro anti-viral activity for both HIV-1 and FIV. Preliminary pharmacokinetic studies in cats demonstrated that subcutaneously injected epiBr was rapidly absorbed, completely metabolized, and nontoxic. Metabolites were excreted in both urine and feces, with the latter having the most complex pattern of breakdown products. Cats were then divided into four groups; two groups were infected with FIV and two uninfected. Two groups, one infected and one uninfected were treated on 5 consecutive days of weeks 0, 4, 8, 12 and 16 with epiBr. The remaining two groups were mock treated with the drug vehicle alone. Treatment started 1 week prior to infection and extended for 4 weeks after infection. Cats were observed for 20 weeks post-FIV infection. Infected cats had identical decreases in blood neutrophil and lymphocyte counts following, regardless of whether they were treated with epiBr or vehicle alone. The CD4/CD8 T-cell ratio was decreased following FIV exposure, but was significantly more decreased for the epiBr treated animals from week 2 post-infection onward. CD4+ T cells were decreased in FIV-infected cats treated with epiBr compared to their untreated cohort, while CD8+ T cells tended to be higher in treated animals. FIV infected cats that were treated with epiBr had over one-log higher virus loads at week 2 post-infection than non-epiBr treated cohorts. In spite of this enhanced initial viremia, the subsequent levels of virus in the blood were significantly lower in epiBr treated versus untreated animals. EpiBr treated cats had significantly higher FIV-p24 antibody responses than control cats receiving vehicle alone, although primary and secondary antibody responses to a T-cell dependent non-FIV antigen, keyhole limpet hemocyanin (KLH), were unaffected. EpiBr treatment significantly decreased the expected FIV-induced suppression of IL-12 p40 mRNA levels in peripheral blood mononuclear cells (PBMCs) observed at weeks 4, 5, 8, 9 and 16 post-infection, but had no influence on FIV-induced changes in IL-4, IL-6, IL-10, IFN-gamma, MIP-1alpha and RANTES.     

No evidence of vertical transmission of naturally acquired feline immunodeficiency virus infection.

A naturally occurring feline immunodeficiency virus (FIV) infection in a closed breeding colony of cats, was studied for a period of 9 months. The colony consisted of 25 adult cats, of which six proved to be infected with FIV as judged by serological examination and virus isolation. In all, 48 kittens were monitored for levels of antibodies against FIV during their first 6 months of life. All the kittens (n = 30) born of FIV-infected queens showed maternal antibodies against FIV, although these declined to undetectable levels by the age of 5 months. Antibodies against FIV were not shown in any of 18 kittens born of FIV-negative queens. An attempt to isolate the virus from 12 kittens between 2 and 6 weeks of age did not succeed. None of the cats in the colony seroconverted during the observation period. In conclusion, neither vertical nor horizontal transmission of FIV infection were demonstrated in the colony during the 9-month investigation period.     

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.     

Distribution of immune cells in the female reproductive tract in uninfected and FIV infected cats

Cell-free and cell-associated FIV effectively cross the mucosa of the feline female reproductive tract. To identify possible cellular targets of FIV and to characterize changes in mucosal immunity after infection, we examined the types and numbers of immune cells residing in the reproductive tracts of control and intravaginally FIV-infected cats. Sections of the vestibule, vagina, cervix, uterus, and ovaries, were examined by immunohistochemistry for CD4+ and CD8+ T lymphocytes, CD22+ B lymphocytes, CD1a+ dendritic cells, and CD14+ macrophages. The reproductive tract of uninfected cats contained substantial numbers of CD8+ T lymphocytes, CD4+ T lymphocytes and macrophages, as well as moderate numbers of CD1a+ dendritic cells, and few B lymphocytes. The most prominent change between FIV- and FIV+ cats was a marked decrease in the concentration of CD4+ T lymphocytes resulting in inverted CD4+:CD8+ ratios throughout the reproductive tract of infected cats. There was also a trend towards increasing numbers of CD1a+ dendritic cells in the intravaginally-infected FIV+ cats, and decreasing numbers of macrophages and CD22+ B lymphocytes. This study indicates that similar to the peripheral immune system, FIV infection is associated with CD4+ cell loss and reduced CD4+:CD8+ ratios in the female reproductive mucosal tissue.     

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.     

Neoplasia associated with feline immunodeficiency virus infection in cats of southern California.

Between 1988 and 1991, feline immunodeficiency virus (FIV) infection status was evaluated in 1,160 cats examined at an oncology referral and general practice in Los Angeles, California. Twenty-nine (2.5%) cats were FIV positive. Neoplasia was present in 18 of the 29 (62%) cats. Sampling for neoplasia was intentionally biased in the oncology referral group. However, 33% (6/18) of FIV-infected cats with neoplasia originated from the general practice. Three neoplastic processes were observed; myeloproliferative disease (MPD; 5/18), lymphoma (LSA; 5/18), and squamous cell carcinoma (SCC; 7/18). One cat had LSA and SCC. Extranodal sites of LSA were common (66%) in FIV-infected cats. Sites of LSA were submandibular and mesenteric lymph nodes, liver, kidneys, periorbital area, and diffuse (heart, pancreas, bladder). Sites of SCC were sublingual (n = 2), nasal planum (n = 3), nasal planum and eyelids (n = 1), and mandible (n = 2). Feline leukemia virus co-infection was observed in 17% (5/29) of FIV-infected cats. The FIV-infected cats with MPD were young (range, 8 months to 13 years; median, 4 years) and had short survival duration (2, 6, 21, 134, 249 days) even in response to aggressive treatment. The FIV-infected cats with LSA were older (median age, 8 years; range, 4 to 14 years) and survived 60 days if untreated. Cats administered chemotherapy survived 39, 45, 217, and 243 days; the latter 2 cats had partial remission of 2 months' duration. Older FIV-infected cats had SCC (median age, 12 years; remission range, 7 to 16 years) because of more frequent association of both diseases in older cats with outdoor environment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative study of the plasma globulin level, CD21(-) B-cell counts and FOXP3 mRNA expression level in CD4(+) T-cells for different clinical stages of feline immunodeficiency virus infected cats

Feline immunodeficiency virus (FIV) infection leads to hypergammaglobulinemia through mechanisms that remain poorly understood. We investigated changes in plasma globulin level, B cells, and T cells with progression of the clinical stage of FIV-infected cats. We classified FIV-infected cats into the stage of Asymptomatic carrier (AC) and AIDS-related complex (ARC) based on the clinical symptoms, and measured the plasma globulin level, the CD4(+) T-cell counts, and analyzed surface markers of B cells. We investigated the relationship between the plasma globulin level and regulatory T cells (Tregs) using the Forkhead box P3 (FOXP3) mRNA expression level. In FIV-infected cats, the plasma globulin level and the surface immunoglobulin (sIg)(+) CD21(-) B-cell counts were increased, whereas the CD4(+) T-cell counts were decreased compared with specific-pathogen free (SPF) cats. The mRNA expression of Blimp-1 (master gene of plasma cells) was increased in peripheral blood, and the FOXP3 mRNA expression level was decreased in CD4(+) T-cells. These immunological changes were marked in the ARC stage. These data indicate that the decrease of Tregs and the increase of plasma cells lead to hypergammaglobulinemia.     

Constitutive expression of types 1 and 2 cytokines by alveolar macrophages from feline immunodeficiency virus-infected cats

Evidence suggests that feline immunodeficiency virus (FIV), causes pulmonary immunodeficiency. The overall objective of this study was to explore FIV-induced alterations in cell counts and cytokine gene expression in the pulmonary compartment during the acute stage infection. Bronchoalveolar lavage (BAL) cells were collected from FIV-infected and control cats at 0, 4, 10, and 16 weeks post-FIV infection for phenotype and cytokine analysis. The major change in BAL cellular populations following FIV-infection was the development of a neutrophilia. Total BAL cell counts and relative numbers of alveolar macrophages (AM), eosinophils, and lymphocytes remained similar in both groups. The RT-qcPCR analyses of AM purified from BAL showed constitutive expression of TNFalpha, IL6 and IL10 mRNAs that peaked during the acute stage of infection then declined. The TNFalpha and IL6 bioactive protein secretion showed a similar response. In contrast, IFNgamma expression increased progressively with time after infection and paralleled a progressive increase in FIV-gag mRNA in AM. The IL12 p40 expression also differed from the other cytokines in that there was a progressive decrease in the number of cats with AM IL12 expression following FIV infection. Infection of AM in vitro with FIV also caused an increase in TNFalpha and IL6 mRNA and bioactive protein suggesting that the increased cytokine response by AM following infection of cats with FIV is an intrinsic characteristic of FIV-infected AM. In summary, pulmonary immune changes seen in FIV-infected cats are similar to those seen in HIV-infected human patients.     

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.     

Feline immunodeficiency virus infection in cats of Japan

A seroepidemiologic survey for feline immunodeficiency virus (FIV) infection was conducted in Japan. Between June and December 1987, individual sera (n = 3,323) were submitted by veterinary practitioners from many parts of the country. Specimens were from 1,739 cats with clinical signs suggestive of FIV infection and from 1,584 healthy-appearing cats seen by the same practitioners. The overall FIV infection rate among cats in Japan was 960/3,323 cats (28.9%). The infection rate was more than 3 times higher in the clinically ill cats, compared with that in the healthy cats of the same cohort (43.9 vs 12.4%). Male cats were 1.5 times as likely to be infected as were females. Almost all FIV-infected cats were domestic cats (as opposed to purebred cats). Complete clinical history was available for 700 of 960 FIV-infected cats. Of these 700 FIV-infected cats, 626 (89.4%) were clinically ill, and the remainder did not have clinical signs of disease. The mean age at the time of FIV diagnosis for the 700 cats was 5.2 years, with younger mean age for males (4.9 years) than for females (5.8 years). Most of the infected cats (94.7%) were either allowed to run outdoors or had lived outdoors before being brought into homes. The mortality for FIV-infected cats during the 6 months after diagnosis was 14.7%, and the mean age at the time of death was 5.7 years. Concurrent FeLV infection was seen in 12.4% of the FIV-infected cats, but this was not much different from the historical incidence of FeLV infection in similar groups of cats not infected with FIV.(ABSTRACT TRUNCATED AT 250 WORDS)     

Is AZT/3TC therapy effective against FIV infection or immunopathogenesis?

In vitro and in vivo prophylactic and therapeutic efficacy of AZT/3TC treatment was evaluated against feline immunodeficiency virus (FIV) infection. In vitro studies utilized FIV-infected peripheral blood mononuclear cells (PBMCs) or FIV-infected T-cell lines treated with AZT (azidothymidine) alone, 3TC alone, or AZT/3TC combination and tested for anti-FIV activity and drug toxicity. AZT/3TC combination had additive to synergistic anti-FIV activities in primary PBMC but not in chronically infected cell lines. In vivo studies consisted of four treatment groups (n=15) of SPF cats receiving AZT/3TC combination (5-75 mg/kg/drug PO BID for 8 or 11 weeks) and one control group (n=9) receiving oral placebo. Group I (n=6, 150 mg/kg/drug/day) was treated starting 3 days pre-FIV inoculation, whereas Group II (n=3, 150 mg/kg/drug/day) and Group III (n=3, 100 mg/kg/drug/day) treatments were simultaneous with FIV inoculation. Group IV treatment (n=3, 100 mg/kg/drug/day) was initiated 2 weeks post-FIV inoculation. All cats were monitored for drug toxicity and FIV infection. Eighty-three percent of cats in Group I and 33% of cats in Groups II and III were completely protected from FIV infection. A significant delay in infection and antibody seroconversion was observed in all unprotected cats from Groups I, II and III. Group IV cats had only a slight delay in FIV antibody seroconversion. Adverse drug reactions (anemia and neutropenia) were observed at high doses (100-150 mg/kg/drug/day) were reversible upon lowering the dose (20 mg/kg/drug/day). In contrast, AZT/3TC treatment had no anti-FIV activity in chronically infected cats. Furthermore, severe clinical symptoms caused by adverse drug reactions were observed in some of these cats. Overall, AZT/3TC treatment is effective for prophylaxis but not for therapeutic use in chronically FIV-infected cats.