Feline Immunodeficiency Virus Infected Cats Research Articles

Cytokine Modulation of the Innate Immune Response in Feline Immunodeficiency Virus–Infected Cats

In vitro data suggest that innate immune function in human immunodeficiency virus type 1-infected patients is compromised; however, in vivo studies are lacking. Feline immunodeficiency virus (FIV) infection in cats provides an excellent model to explore innate immune function in vivo. The innate response against Listeria monocytogenes is well understood, making it a useful immune probe. Recombinant L. monocytogenes carrying eukaryotic expression plasmids for feline tumor necrosis factor (TNF)- alpha , interleukin (IL)-10, interferon (IFN)- gamma , and IL-15 were created to determine whether specific cytokines would modulate innate immune function. L. monocytogenes was delivered subcutaneously, and local lymph nodes were evaluated for size, cell subpopulations, and L. monocytogenes burden. Two months later, memory responses were evaluated by IFN- gamma enzyme-linked immunospot assay. FIV-positive cats had significantly less lymph-node enlargement and a greater L. monocytogenes burden than FIV-negative control cats. TNF- alpha improved listericidal activity in FIV-negative control cats but not in FIV-positive cats, whereas IL-10 modestly reduced function in FIV-negative control cats. IFN- gamma improved memory responses but not clearance of L. monocytogenes. IL-15 improved innate function in FIV-positive cats and increased the percentage of natural killer cells. Lentivirus infection impairs innate immune function in vivo, and IL-15 can significantly restore function. We hypothesize that altered dendritic-cell function and increased regulatory T cell activity may underlie the innate immune defect in HIV infection.

Feline Immunodeficiency Virus Depletes Naïve (CD45RA+) CD4+ Lymphocytes from the Blood and Lymph Nodes of Domestic Cats during Acute Pediatric Infection.

Feline immunodeficiency virus (FIV) is an immunosuppressive lentivirus of domestic cats that serves as an animal model for the pathogenesis of CD4+ lymphopenia and thymus dysfunction in HIV infected humans. During most cases of adult and pediatric HIV infection, naïve CD4+ T lymphocytes recognized by the expression of the RA isoform of the leukocyte common antigen (CD45RA) are infected at a lower level than memory CD4+ T− lymphocytes; however, children with rapidly progressive disease due to thymic insufficiency harbor high levels of HIV within the CD45RA+ subpopulation. In FIV infected cats, the fate of naïve CD4 lymphocytes is unknown due to the lack of specific markers. Recently, a mAb (755) was reported to recognize the feline homologue to CD45RA, allowing the enumeration of naïve CD4 and CD8 lymphocytes in cats. The purpose of this study was to characterize the fate of CD4+CD45RA+ blood cells eight weeks after FIV infection. One-day-old kittens (n=6) were infected with virions either from a wild type clone (JSY3) or mutant ORF-A clone at equivalent reverse transcriptase units and compared to historical control data. Eight weeks after inoculation, the percentages of CD4+ and CD8+ cells belonging to the CD45RA+ subpopulation were measured by two-color flow cytometry. Both FIV inocula were associated with a reduction in total CD4+ lymphocytes from a median of 13% in controls to 8% in infected cats (P=0.004), contributing to a reduction in the CD4:CD8 ratio from 2.45 in controls to 0.76 in infected cats (P=0.007). The decline in CD4+ lymphocytes was attributable to a disproportionate loss of CD4+CD45RA+ cells: 69% of CD4+ cells were CD45RA+ in controls, as compared to 7% in FIV infected cats (P=0.004). In contrast, naïve CD8+ lymphocytes did not change significantly with FIV infection (67% of CD8+ cells were CD45RA+ in FIV infected cats as compared to 80% in controls). The distribution of CD45RA+ cells in the lymph nodes of FIV infected cats mirrored those in the blood. Together, these data suggest that acute FIV infection results in a rapid depletion of naïve CD4 lymphocytes throughout the blood and secondary lymphoid tissues, while proportions of naïve CD8 lymphocytes remain unchanged. CD4+CD45RA+ cells may be depleted during pediatric FIV infection through lytic infection or a transition to a memory phenotype lacking CD45RA.

Generation of Feline Dendritic Cells Derived from Peripheral Blood Monocytes for In Vivo Use

Dendritic cells (DCs) are professional antigen-presenting cells that can prime T cells and polarize the cellular immune response. Because Th1-type immune responses have been connected to success in combating viral infection, a promising therapeutic application of DCs would be their differentiation in vitro and injection back into the host to boost an immune response in infected animals. This study was aimed both at developing a protocol to cultivate feline DCs in the absence of exogenous proteins for their use in vivo and at investigating what might be the most appropriate stimulus to induce their maturation in vitro and finding correlates of maturation. We generated DCs from peripheral blood monocytes in the presence of feline interleukin-4 and granulocyte-macrophage colony stimulating factor, and after 5 days their maturation was induced with either lipopolysaccharide, human recombinant tumor necrosis factor alpha, poly(I:C), or activated feline platelets. After 48 h, their CD14, CD1a, major histocompatibility complex class II, and B7.1 surface expression was analyzed in parallel with their ability to uptake antigen or prime a mixed leukocyte reaction. The results presented show that feline DCs cultured in autologous plasma differentiate and are able to mature in the presence of stimuli similar to the ones currently used for other species. The present work sets the grounds for future use of DCs obtained by the protocol described for in vivo vaccination and immunotherapy of feline immunodeficiency virus-infected cats.

Peptide mapping of feline immunodeficiency virus by IFN-gamma ELISPOT.

Interferon-gamma (IFN-gamma) enzyme-linked immunospot (ELISPOT) has become an important tool in studying antigen-specific T lymphocyte responses. Soluble peptides can be used to map T-cell epitopes, providing information that is useful in the design and evaluation of vaccines as well as studies of immunopathogenesis. To date, this assay has not been widely utilized in feline immunodeficiency virus (FIV) research. We have developed a feline IFN-gamma ELISPOT assay and used it to determine FIV-specific T-cell epitopes recognized by infected cats. A panel of 331 peptides, 15 amino acids in length and overlapping by 10 residues was synthesized. The peptide library spanned the FIV structural (Gag), envelope (Env), reverse transcriptase (RT), and open-reading-frame A (OrfA) proteins. Initially, 34 pools, containing 7-10 peptides each were screened by IFN-gamma ELISPOT against peripheral blood mononuclear cells (PBMC) from eight cats chronically infected with the NCSU(1) molecular clone of FIV and four uninfected control cats. Individual peptides from pools recognized by FIV+ cats were then evaluated and optimal peptides were combined into pools representing Gag, Env, RT, and OrfA. A higher percentage of FIV infected cats were identified as responders against the peptide pools when using fresh PBMC as compared to cryopreserved PBMC. In vitro restimulation of cryopreserved PBMC with the peptide pools improved the sensitivity of the assay to similar levels as observed from fresh samples. Individual peptides used in the pools were generally found to stimulate CD8+ T-cells more efficiently than CD4+ T-cells. Comparison of the peptide sequences to representative FIV sequences from clades A-D showed conservation was high among Gag and RT peptides, variable among Env peptides and low for OrfA peptides. The IFN-gamma ELISPOT assay and FIV-specific peptide pools we describe here will be useful in assessing cell-mediated responses to experimental FIV vaccines.

Escalating morphine exposures followed by withdrawal in feline immunodeficiency virus-infected cats: a model for HIV infection in chronic opiate abusers

Opiate abuse is a risk factor for human immunodeficiency virus (HIV) infection. Because the direct effects of opiates on HIV infection are difficult to determine epidemiologically, animal models of lentivirus infection are relied upon to study the effects of opiates in the absence of confounding factors. Morphine, the predominant metabolite of heroin, is used in most experimental systems examining heroin abuse. In this study, morphine treatment of feline immunodeficiency virus (FIV)-infected cats modeled a typical pattern of escalating drug use interspersed with withdrawals. Plasma cortisol levels were measured for evidence of stress associated with morphine withdrawal. In the morphine-treated cats, cortisol levels peaked at time points corresponding to morphine withdrawal and returned to baseline levels during treatment and several weeks after the final withdrawal. Morphine-treated cats displayed clear behavioral and physical signs of opiate exposure and evidence of withdrawal when the drug was stopped. Morphine-exposed cats did not experience enhanced severity of FIV-related disease; in fact, morphine demonstrated a protective effect on FIV-associated changes in brainstem auditory evoked potentials. Our research suggests that opiate exposure is unlikely to adversely affect the progression of acute lentivirus infection and might be beneficial in controlling associated neurological disease.

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

16α-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-γ, MIP-1α and RANTES.

In vivo antiretroviral activity of stampidine in chronically feline immunodeficiency virus-infected cats.

Here we report the antiretroviral activity of the experimental nucleoside reverse transcriptase inhibitor (NRTI) compound stampidine in cats chronically infected with feline immunodeficiency virus (FIV). Notably, a single oral bolus dose of 50 or 100 mg of stampidine per kg resulted in a transient >/=1-log decrease in the FIV load of circulating peripheral blood mononuclear cells in five of six FIV-infected cats and no side effects. A 4-week stampidine treatment course with twice-daily administration of hard gelatin capsules containing 25 to 100 mg of stampidine per kg was also very well tolerated by cats at cumulative dose levels as high as 8.4 g/kg and exhibited a dose-dependent antiretroviral effect. One of three cats treated at the 25-mg/kg dose level, three of three cats treated at the 50-mg/kg dose level, and three of three cats treated at the 100-mg/kg dose level (but none of three control cats treated with placebo pills) showed a therapeutic response, as evidenced by a >/=1-log reduction in the FIV load in peripheral blood mononuclear cells within 2 weeks. The previously documented in vitro and in vivo antiretroviral activity of stampidine against primary clinical human immunodeficiency virus type 1 isolates with genotypic and/or phenotypic NRTI resistance, together with its favorable animal toxicity profile, pharmacokinetics, and in vivo antiretroviral activity in FIV-infected cats, warrants further development of this promising new NRTI compound.

CD8+ T cells from feline immunodeficiency virus (FIV) infected cats suppress exogenous FIV replication of their peripheral blood mononuclear cells in vitro.

Feline immunodeficiency virus (FIV) isolates from domestic cats have been classified into five subtypes, designated A, B, C, D and E. Although many FIV-infected cats may have frequent contact with multiple strains of FIV, they usually become infected with a single FIV subtype. In the present study, we demonstrate that peripheral blood mononuclear cells (PBMC) of FIV infected cats were resistant to exogenous FIV (second virus) replication in vitro and that the resistance of these PBMC was mediated by CD8+ T cells. In cats with a low anti-FIV activity of CD8+ T cells, the proviral DNA of the second virus inoculated into PBMC was detected intracellularly, and both the second and the originally infecting strain (original virus) were produced in the culture supernatant. In contrast, in cats with a high anti-FIV activity of CD8+ T cells, both the proviral DNA of the second virus and the original virus were detected in PBMC intracellularly, but neither virus was produced in the culture supernatant. However, when PBMCs from these cats were depleted of CD8+ T cells, the RNA of both viruses was detected in the culture supernatant. These results suggest that CD8+ T cells inhibit the late phase of FIV replication after viral integration. Moreover, the inhibition was also effective against FIV strains of different subtypes from that of the original strain. It appears that the CD8+ T cell-mediated immune response plays important roles in the maintenance of an asymptomatic state in FIV-infected cats and their resistance to superinfection.

Productive infection of the bone marrow cells in feline immunodeficiency virus infected cats.

Bone marrow stromal cells (BMSC) from cats experimentally infected with feline immunodeficiency virus (FIV) were shown to contain FIV provirus using polymerase chain reaction and viral products were detected in culture supernatant using reverse transcriptase and enzyme linked immunosorbent assay techniques. Peripheral blood mononuclear cells from FIV-free cats co-cultured with infected bone marrow cells became productively infected with FIV. Such evidence supports the hypothesis that BMSC are a reservoir for FIV. Furthermore, BMSC produced virions capable of infecting susceptible cells and may represent an important source of infectious virus to cells of the macrophage lineage and/or hemopoietic progenitor cells, both of which ultimately become widely disseminated throughout the body.

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 TNFα, IL6 and IL10 mRNAs that peaked during the acute stage of infection then declined. The TNFα and IL6 bioactive protein secretion showed a similar response. In contrast, IFNγ 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 TNFα 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.

T cells overexpressing interferon-gamma and interleukin-10 are found in both the thymus and secondary lymphoid tissues of feline immunodeficiency virus-infected cats.

Similar to human immunodeficiency virus type 1, feline immunodeficiency virus (FIV) replicates in the thymus of infected animals, causing marked alteration in thymic lymphocyte subpopulations. The immune phenotype and cytokine patterns in the thymus and secondary lymphoid tissues of FIV-infected cats were investigated. FIV infection caused an acute-stage transient reduction in CD4CD8 double-positive thymocytes, a marked increase in CD8 single-positive thymocytes, and formation of thymic B cell lymphoid follicles. Interferon (IFN)-gamma and interleukin (IL)-10 mRNA were up-regulated in both the thymus and lymph nodes of FIV-infected cats. Analysis of purified CD4 and CD8 cells revealed that CD4 cells produced most of the IL-10, whereas IFN-gamma was produced by both subsets. Quantitative-competitive reverse-transcription polymerase chain reaction analysis revealed that thymocytes, especially CD4CD8 thymocytes, had much greater levels of gag mRNA than did lymph node T cells. Thus, overexpression of IFN-gamma and IL-10 is a feature of the thymus and secondary lymphoid tissues of FIV-infected cats.

Elevated interleukin-10-to-interleukin-12 ratio in feline immunodeficiency virus-infected cats predicts loss of type 1 immunity to Toxoplasma gondii.

Similar to human immunodeficiency virus, feline immunodeficiency virus (FIV) induces immunodeficiency and enhanced susceptibility to secondary pathogens. To explore cytokine alterations in lentivirus immunodeficiency, constitutive mRNA expression was measured in lymph nodes of healthy and FIV-infected cats before and after challenge with Toxoplasma gondii. Cytokine mRNA expression was similar in control and FIV-infected cats during the first 10 weeks after infection. At 16 weeks, interferon (IFN)-gamma, tumor necrosis factor-alpha, and interleukin (IL)-10 mRNA were increased in FIV-infected cats. Challenge with T. gondii induced an increase in IL-2, IFN-gamma, and IL-12 in the lymph nodes of control cats, whereas IFN-gamma and IL-10 but not IL-2 or IL-12 increased in the lymph nodes of FIV-T. gondii coinfected cats. These results indicate that FIV immunodeficiency may derive from a failure to generate an IL-12-dependent type 1 response and that an elevated level of IL-10 mRNA expression is a predictor of lentivirus immunodeficiency.

Value of α1-acid glycoprotein in the diagnosis of feline infectious peritonitis

Feline infectious peritonitis (FIP) is notoriously difficult to differentiate from the many other diseases with similar clinical signs and at present the only conclusive diagnostic test is the histopathological examination...

Estudo clínico da síndrome de imunodeficiência adquirida em gatos domésticos de São Paulo

Com a finalidade de estudar a magnitude da ocorrência do vírus da leucemia felina (VLF) e do vírus da imunodeficiência dos felinos (VIF) entre os felinos domésticos de São Paulo, 401 animais de ambos os sexos, idade e raças variadas, foram submetidos à pesquisa de anticorpos humorais (VIF) e de antígenos virais solúveis (VLF) através do teste imunoenzimático - ELISA (Feline Leukímia Virus Antígen / Feline Immunodeficiency Virus Antibory - CITE® - Agritech Systems Inc.). Desses, 123 eram felinos sadios e os demais 278 animais eram felinos doentes atendidos no Departamento de Clínica Médica/Hospital Veterinário da FMVZ/USP. Foram observados 8 (6,5%) reagentes ao VIF entre os felinos sadios e 39 (14%) entre os gatos doentes. Em relação ao VLF, 2 (1,6%) dos animais sadios e 30 (10,8%) entre os gatos doentes foram reagentes ao teste imunoenzimático e apenas um animal foi reagente a ambos os vírus. A infecção pelo VIF foi mais freqüente entre os machos, quando comparada às fêmeas, na proporção de 4:1, não tendo sido, no entretanto, observada diferença entre machos e fêmeas infectados em relação ao VLF. As infecções oportunistas, como a causada por Haemobartonella felis, foram as doenças associadas mais freqüentemente observadas tanto nos felinos VLF positivos quanto nos VIF positivos. Em relação aos tumores, a forma mediastinal do linfoma foi a mais freqüente entre os felinos VLF positivos. As demais condições mórbidas que se associaram à infecção pelos dois Retrovirus foram de natureza e freqüência variáveis. A idade média dos animais infectados pelo VIF foi de 4,4 + 3,0 anos e dos felinos infectados pelo VLF, de 2,4 + 1,7 anos. Todos os animais reagentes e sintomáticos não sobreviveram mais do que dois anos. Por outro lado, não houve nenhum óbito entre os animais assintomáticos infectados por qualquer um dos Retrovirus durante o mesmo período de observação, demonstrando que operíodo de pré-patência pós-infecção pode ser bastante longo.

Interstitial lung disease in feline immunodeficiency virus ( FIV) infected cats

Postmortem bronchoalveolar lavage of feline immunodeficiency virus-infected cats indicated an alveolitis process, and histological examination of their lungs confirmed the occurrence of alveolitis, parenchymatous lymphoplasmocytic infiltration and myomatosis. Similar lymphoid interstitial pneumonitis has been described in human and animal lentiviral diseases: lymphocytic interstitial pneumonitis in hiv-1-infected human beings, and maedi in sheep infected by the maedi-visna virus. Such lymphoid interstitial pneumonitis may thus be a common feature of lentiviral infections.

Serum Concentration of Circulating Immune Complexes in Cats Infected with Feline Immunodeficiency Virus Detected by Immune Adherence Hemagglutination Method.

Circulating immune complexes (CIC) in the sera from 45 clinically healthy cats and 23 feline immunodeficiency virus (FIV) infected cats were measured by an immune adherence hemagglutination (IAHA) method. The level of CIC in the sera from FIV sera-negative healthy cats was 47.2 +/- 47.3 micrograms/ml when expressed as heat aggregated feline IgG equivalent value in IAHA reactivity. On the other hand, the level of CIC in the sera from FIV infected cats was 757.4 +/- 910.5 micrograms/ml, which was significantly higher than that of healthy ones. CIC levels of 11 symptomatic cats and 12 asymptomatic ones were 837.8 +/- 1138.2 micrograms/ml and 683.0 +/- 684.2 micrograms/ml, respectively. These results showed that IAHA method was reliable to detect CIC levels of cat sera and that CIC levels in the sera of cats infected with FIV were higher than those of healthy ones.

Cortical neuronal cytoskeletal changes associated with FIV infection.

HIV-1 infection is often complicated by central nervous system (CNS) dysfunction. Degenerative neuronal changes as well as neuronal loss have been documented in individuals with AIDS. Feline immunodeficiency virus (FIV) infection of cats provides a model for both the immune and the central nervous system manifestations of HIV infection of humans. In this study we have examined neurons in the frontal cortex of feline immunodeficiency virus-infected cats and controls for immunoreactivity with SMI 32, an antibody recognizing a non-phosphorylated epitope on neurofilaments. We noted a significant increase in the number of immunoreactive pyramidal cells in infected animals compared to controls. The changes seen in the neuronal cytoskeleton as a consequence of the inoculation with FIV were similar to those seen in humans undergoing the normal aging process as well as those suffering from neurological diseases, including Alzheimer's and dementia pugilistica. The changes we noted in the feline brain were also similar to that reported in animals with traumatic injuries or with spontaneously occurring or induced motor neuron diseases, suggesting that the increase in reactivity represents a deleterious effect of FIV on the central nervous system.

Primary and Secondary Toxoplasma gondii Infection in Normal and Feline Immunodeficiency Virus-Infected Cats

Normal and asymptomatic feline immunodeficiency virus (FIV)-infected adult cats were inoculated orally with Toxoplasma gondii tissue cysts to assess differences in clinical disease, T. gondii serologic test results, hematologic results, and oocyst shedding. There was no difference between FIV-naive and FIV-infected cats in terms of clinical illness and duration of oocyst shedding following primary exposure. Both groups of cats developed significant decreases in neutrophil counts following primary inoculation with T. gondii; FIV-infected cats that were neutropenic prior to inoculation with T. gondii developed the most profound decreases in neutrophil numbers. Both FIV-naive and FIV-infected cats became lymphopenic during acute T. gondii infection; however, only FIV-naive cats developed lymphocytosis in the recovery stage. FIV-infected cats had lower total CD4+ and higher total CD8+ T-lymphocyte counts than FIV-naive cats prior to inoculation with T. gondii, but changes in these lymphocyte subsets were similar between groups of cats during the first several weeks after inoculation. Toxoplasma gondii infection had neither an ameliorating nor enhancing effect on T-lymphocyte subset abnormalities in FIV-infected cats during acute or chronic infection. Both groups of cats developed comparable levels of T. gondii-specific IgM and IgG antibodies and T. gondii antigen-specific lymphocyte blastogenic responses following primary inoculation. Both groups of cats were fed T. gondii tissue cysts 66 wk following primary exposure and both groups were solidly immune as evidenced by a lack of oocyst shedding and only minor changes in IgM but not IgG antibodies.

Quantification of lymphadenopathy in experimentally induced feline immunodeficiency virus infection in domestic cats

Nine cats experimentally infected with feline immunodeficiency virus (FIV) and six FIV-negative cats were necropsied to assess the effect of FIV infection on lymph nodes. The FIV infected cats were inoculated with 10 5 TCID 50 21–22 weeks previously. The combined weights of all lymph nodes and the combined lymph node to organ weight ratios were significantly greater in FIV-infected cats when compared to uninfected cats. Additionally, by examining all nodes in the body, a regionally severe lymphadenopathy in FIV-infected cats was evident involving the lymph nodes of the hindlimb, forelimb, and head, in decreasing order of severity, with little evidence of enlargement in lymph nodes of the alimentary tract. Use of 99% confidence intervals showed that 9 9 FIV infected cats had enlarged lymph nodes of the hindlimb and forelimb region. In contrast, 7 9 and 3 9 FIV-infected cats exhibited enlargement of the nodes of the head region and alimentary tract, respectively. Similarly the combined weights of both left and right popliteal lymph nodes were enlarged in 9 9 FIV-infected cats whereas 0 6 in uninfected cats were not. The enlargement of the popliteal lymph nodes observed at necropsy was reflected microscopically by an increase in the size and number of germinal centres and an increase in the number of plasma cells, especially in the medullary cords. Because of the regional variation in lymph node size and numbers, it is suggested that the popliteal lymph node is a good indicator node for the assessment of lymph node status in FIV infection.

Tumor necrosis factor-α responses are depressed and interleukin-6 responses unaltered in feline immunodeficiency virus infected cats

Feline immunodeficiency virus (FIV), a lentivirus similar to HIV, causes an acquired immunodeficiency syndrome in cats. Similar to human immunodeficiency virus (HIV), the pathogenesis of FIV is associated with dysregulation of the cytokine network. While alterations in tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression have been reported in HIV-infected patients, changes attributable to HIV and those caused by cofactors such as secondary infections cannot always be readily distinguished. This study evaluated the effect of FIV infection on TNF-α and IL-6 production in cats not exposed to other potential cofactors such as secondary infections. TNF-α and IL-6 activities were evaluated in bronchoalveolar lavage (BAL) cells from FIV-infected and uninfected specific pathogen free (SPF) cats. Supernatants from lipopolysaccharide (LPS)-stimulated BAL cells from uninfected SPF cats had high levels of TNF-α and IL-6 activity, while stimulated BAL cell supernatants from FIV-infected SPF cats had significantly lower levels of TNF-α but unaltered IL-6 activity. Similarly, Con A/phorbol myristate acetate (PMA) stimulated non-adherent (NA-) peripheral blood mononuclear cells (PBMC) from FIV infected cats synthesized less TNF-α than similarly treated NA-PBMC from uninfected cats. Feline immunodeficiency virus could be recovered from the culture supernatants of BAL cells from infected cats by co-cultivation with susceptible lymphocytes. In situ hybridization identified FIV mRNA in a small fraction of alveolar macrophages in the BAL cell cultures. Considering that these SPF cats have been infected with FIV for up to 3 years, yet remain asymptomatic and have no evidence of secondary infections, the present data suggest that the deficiency in TNF-α production by BAL cells and NA-PBMC is an intrinsic characteristic of the FIV infection.