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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 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.
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
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
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.
Materials and methods • Blood samples collected • Genomic DNA was isolated using PCR • Three negative controls • Two positive controls
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
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
How can we use lentiviruses in research? FIV and Research
What kinds of research are done with Lentiviruses? • FIV coevolution with feline communities • Methamphetamines and HIV/FIV • Gene Therapy
Life cycle web.uct.ac.za/.../teaching/notes/retro.htm
Gene therapy vectors • FIV • SIV • HIV-1 • HIV-2
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
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
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?
How accessible is this stuff? Lentigen