Pathogenesis of Feline Immunodeficiency Virus Infection

Colorado State University, Fort Collins CO

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Multiple lines of evidence indicate that the critical events determining the host/lentivirus relationship after mucosal exposure: (a) occur within days of exposure; (b) involve the innate immune system and its juncture with the adaptive immune system; and (c) influence virus set point potentially determining whether or not the infection becomes progressive. While the early local innate immune response may be pivotal in early viral containment, it is difficult to access in humans exposed to HIV therefore animal lentivirus immunodeficiency models assume special relevance. Feline immunodeficiency virus (FIV), the feline counterpart of HIV and SIV, is transmissible by vaginal, rectal, or oral exposure and can result in the typical host-lentivirus relationships including: (a) typical slowly progressive infection leading to clinical immunodeficiency; (b) rapidly progressive and fatal infection; and (c) poorly understood transient/occult/regressive infection states. Cytokines bridge the innate and acquired immune systems by linking antigen presenting cells with effector lymphocytes. Here we use the FIV model to focus on the early in vivo host/lentivirus interactions to test the hypothesis that augmenting the innate and cell-mediated immune mechanism will produce resistance to mucosal FIV infection. Specifically we will determine: (1) whether manipulation of the early cytokine balance to favor a strong cell-mediated immune response will promote control of transmucosal FIV infection; (2) whether administration of proven stimulators of innate immunity will enhance resistance to mucosal FIV infection; and (3) whether cross priming the cell-mediated immune response by administration of liposome nucleic acid inactivated whole virus will enable animals to contain early mucosal infection. These studies will help provide a rational basis for use of immunmodulatory therapies and help understand the potential for containment, clearance, and immunoprophylaxis in HIV infection. [unreadable] [unreadable]