Lessons from the cat: Feline immunodeficiency virus as a tool to develop intervention strategies against human immunodeficiency virus type 1
Available from: PubMed Central
- "Since investigating the dynamics of the NK cell response in lymph nodes (LN) of HIV-infected or healthy people in response to a microorganism challenge is not feasible, we used the feline immunodeficiency virus (FIV) model to study HIV/AIDS. FIV infection of cats is clinically and immunologically similar to HIV-1 in people –, providing a valuable animal model to investigate the consequences of lentivirus infection on the innate immune response. Because the innate immune response to Listeria monocytogenes (Lm) is well understood (reviewed in ), we used this intracellular pathogen to probe the innate immune system in order to investigate the effects of chronic FIV infection on NK cell function. "
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ABSTRACT: Accumulating evidence suggests that natural killer (NK) cells may have an important role in HIV-1 disease pathogenesis; however, in vivo studies are lacking. Feline immunodeficiency virus (FIV) infection of cats provides a valuable model to study NK cell function in vivo. The immune response against Listeria monocytogenes (Lm) is well characterized, allowing its use as an innate immune probe. We have previously shown that locally delivered IL-15 can improve Lm clearance in FIV-infected animals, and this correlated with an increase in NK cell number. In the present study, chronically FIV-infected and SPF-control cats were challenged with Lm by unilateral subcutaneous injection next to the footpad and then treated with 5-bromo-2'-deoxyuridine (BrdU). The Lm draining and contralateral control lymph nodes were evaluated for NK, NKT, CD4+ and CD8+ T cell number, proliferation, apoptosis, and NK cell function. Listeria monocytogenes burden was also assessed in both control and Lm draining lymph nodes. NK, NKT, CD4+ T and CD8+ T cells in the Lm-challenged lymph node of FIV-infected cats did not increase in number. In addition, after Lm challenge, NK cells from FIV-infected cats did not increase their proliferation rate, apoptosis was elevated, and perforin expression was not upregulated when compared to SPF-control cats. The failure of the NK cell response against Lm challenge in the draining lymph node of FIV-infected cats correlates with the delayed control and clearance of this opportunistic bacterial pathogen.
PLoS ONE 05/2012; 7(5):e37606. DOI:10.1371/journal.pone.0037606 · 3.23 Impact Factor
Available from: Meggan Eileen Craft
- "In domestic cats (Felis catus), FIV infection results in immune pathology, secondary infections , and death. The parallels between human and feline AIDS (FAIDS) have been explored for further understanding of HIV/AIDS transmission, infection, and pathology (Bendinelli et al., 1995; Burkhard and Dean, 2003; Elder et al., 1998, 2010; Henriksen et al., 1995; Stump and VandeWoude, 2007). As with HIV and SIV models, there is considerable variation in transmission, course of infection , and outcome of FIV infections in domestic cats. "
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ABSTRACT: Feline immunodeficiency virus (FIV) infects domestic cats and at least 20 additional species of non-domestic felids throughout the world. Strains specific to domestic cat (FIV(Fca)) produce AIDS-like disease progression, sequelae and pathology providing an informative model for HIV infection in humans. Less is known about the immunological and pathological influence of FIV in other felid species although multiple distinct strains of FIV circulate in natural populations. As in HIV-1 and HIV-2, multiple diverse cross-species infections may have occurred. In the Serengeti National Park, Tanzania, three divergent subtypes of lion FIV (FIV(Ple)) are endemic, whereby 100% of adult lions are infected with one or more of these strains. Herein, the relative distribution of these subtypes in the population are surveyed and, combined with observed differences in lion mortality due to secondary infections based on FIV(Ple) subtypes, the data suggest that FIV(Ple) subtypes may have different patterns of pathogenicity and transmissibility among wild lion populations.
Veterinary Immunology and Immunopathology 06/2011; 143(3-4):338-46. DOI:10.1016/j.vetimm.2011.06.013 · 1.54 Impact Factor
Available from: Brian James Willett
- "Env varies by up to 30 % amongst FIV subtypes (Hosie & Beatty, 2007) and, thus, the preparation of an immunogen capable of inducing broadly neutralizing antibody responses against such diverse isolates of FIV would be of great value to the development of an FIV vaccine. Further, the development of a vaccine against FIV would have implications extending beyond veterinary medicine; FIV is the only non-primate lentivirus that induces AIDS-like symptoms in its natural host and, as such, is a valuable animal model for both prophylactic and therapeutic studies for HIV (Bendinelli et al., 1995; Elder et al., 1998; Okada et al., 1994). Moreover, cats have the advantage of being easier to breed and have shorter life cycles than other animal models currently used for HIV research (Miller et al., 2000). "
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ABSTRACT: Neutralizing antibodies (NAbs) play a vital role in vaccine-induced protection against infection with feline immunodeficiency virus (FIV). However, little is known about the appropriate presentation of neutralization epitopes in order to induce NAbs effectively; the majority of the antibodies that are induced are directed against non-neutralizing epitopes. Here, we demonstrate that a subtype B strain of FIV, designated NG4, escapes autologous NAbs, but may be rendered neutralization-sensitive following the insertion of two amino acids, KT, at positions 556-557 in the fifth hypervariable (V5) loop of the envelope glycoprotein. Consistent with the contribution of this motif to virus neutralization, an additional three subtype B strains retaining both residues at the same position were also neutralized by the NG4 serum, and serum from an unrelated cat (TOT1) targeted the same sequence in V5. Moreover, when the V5 loop of subtype B isolate KNG2, an isolate that was moderately resistant to neutralization by NG4 serum, was mutated to incorporate the KT motif, the virus was rendered sensitive to neutralization. These data suggest that, even in a polyclonal serum derived from FIV-infected cats following natural infection, the primary determinant of virus-neutralizing activity may be represented by a single, dominant epitope in V5.
Journal of General Virology 09/2009; 91(Pt 1):242-9. DOI:10.1099/vir.0.015404-0 · 3.18 Impact Factor
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