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Feline Immunodeficiency Virus

Feline Immunodeficiency Virus. Research involving FIV Nora Zayas and Elisha Lee. FIV as a model for understanding HIV. Model system to study a number of aspects of lentivirus biology including: Virus transmission Pathogenesis Host immune responses Vaccine development.

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Feline Immunodeficiency Virus

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  1. Feline Immunodeficiency Virus Research involving FIV Nora Zayas and Elisha Lee

  2. FIV as a model for understanding HIV • Model system to study a number of aspects of lentivirus biology including: • Virus transmission • Pathogenesis • Host immune responses • Vaccine development.

  3. Similarities and Differences • Both viruses target activated CD4 lymphocytes • FIV contains deoxyuridine pyrophosphatase (DU) • HIV lacks DU, but its function is assumed by Vpr protein • Rev is encoded by both HIV and FIV • Vif protein is also present in both viruses

  4. FIV genome sequences circulating in free-ranging populations of lions • FIV-Ple A, FIV-Ple B, FIV-Ple C • Occurrence of these three strains indicates that the strains have recently converged within the same population • High incidence of FIV (90%) • Presence of the three divergent subtypes provide an opportunity for study

  5. Patterns of proviral strain diversity and occurrence • 349 free-ranging lions representing 13 prides within the Serengeti National Park • Examined three distinct genes – gag, pol-RT, and pol-RNase.

  6. Materials and methods • Blood samples collected • Genomic DNA was isolated using PCR • Three negative controls • Two positive controls

  7. Results • 43% of the pol-RT PCR-positive lions were infected with more than one FIV-Ple strain • FIV-Ple B was the most common (82%) • FIV-Ple A was the rarest (12%) • FIV-Ple C had intermediate prevalence (53%) • Phylogenetic analyses of FIV-Ple sequences

  8. Analysis • Studies of coinfection and superinfection in wild populations will help define the genetic divergence limitations • This genetic divergence is a barrier to vaccine development • Possible outcome of coinfection is the recombination of the subtypes • Coevolution between lion immune systems and FIV-Ple has led to partial adaptation between the virus and its host

  9. How can we use lentiviruses in research? FIV and Research

  10. What kinds of research are done with Lentiviruses? • FIV coevolution with feline communities • Methamphetamines and HIV/FIV • Gene Therapy

  11. Life cycle web.uct.ac.za/.../teaching/notes/retro.htm

  12. Gene therapy vectors • FIV • SIV • HIV-1 • HIV-2

  13. Warning!!!! Hazardous materials!!!! • HIV-1, HIV-2, and SIV are the only primate lentiviruses • HIV-2 and SIV pathogenicity and transmission rates fall far below that of HIV-1. • HIV-2 and SIV viruses can be studied in non-human primates • Provides opportunity for substantial preclinical evaluation • Recombinant DNA Advisory Committee (RAC) has provided guidelines for safety

  14. Why are Lentivectors so fabulous? • Don’t require replication by infected cells for productive infection • Great for in vivo administration • Can transduce stem,dendritic,T-cells, and neurons(when appropriately pseudotyped) • Transduction with high efficiency and transgene expression. • Produce long term effects

  15. How can we use FIV? • Compared to HIV vectors, FIV vector development still in very early stages • HIV has helped cats, so can FIV help humans?

  16. How accessible is this stuff? Lentigen

  17. Thank you for your nice evaluations!!!

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