LB-5. TRIM5 modulates penile mucosal acquisition of simian immunodeficiency virus in rhesus monkeys
Session: Poster Abstract Session: Late Breaker Posters
Saturday, October 22, 2011
Room: Poster Hall B1
Handouts
  • Yeh IDSA poster 2011.pdf (565.9 kB)
  • Background: Although the male genital tract constitutes a major site of HIV-1 invasion worldwide, little is known about the precise routes of viral entry into the male reproductive tract.  Understanding the early events associated with HIV-1 acquisition in the penile mucosa has been hampered by the lack of an animal penile transmission model. 

    Method: Our objective is to develop a simian immunodeficiency virus (SIV)/rhesus monkey penile infection model to study early HIV-1 pathogenesis in men.  To overcome the difficulties of initiating SIV penile infection, we tested the hypothesis that TRIM5 alleles play a role in modulating mucosal acquisition of SIV in Indian-origin rhesus monkeys.  We placed SIVsmE660 (3x 108 SIV RNA copies/ml) atraumatically into the prepuce pouch of rhesus monkeys that are genotyped for TRIM5 alleles.  Plasma SIV RNA levels were prospectively determined weekly using qRT-PCR.  We then enumerated the number of transmitted/founder (T/F) viruses responsible for productive infection using single genome amplification. 

    Result: We exposed 3 groups of male rhesus monkeys (TRIM5 homozygous permissive, heterozygous permissive, and homozygous restrictive, N=6/group) to SIVsmE660 weekly for 12 weeks.  Five of 6 monkeys (83%) became infected in the homozygous permissive group and 5 of 6 monkeys (83%) became infected in the heterozygous permissive group.  Interestingly, no monkeys became infected in the homozygous restrictive group (p= 0.005, Fisher’s exact test).  In monkeys that became infected, a median of 1 T/F virus was transmitted via the penile mucosa. 

    Conclusion: These data demonstrate that TRIM5 plays a critical role in restricting mucosal transmission of SIV and can be exploited to establish a reliable nonhuman primate penile transmission model.  The demonstration that a simplification of viral quasispecies occurred after penile transmission lends credibility to the use of this model for HIV-1 pathogenesis, vaccine, and microbicide research.


    Subject Category: H. HIV/AIDS and other retroviruses

    Wendy Yeh, M.D.1, Srinivas Rao, DVM, PhD2, So-Yon Lim, PhD3, Jinrong Zhang, M.D.3, Peter Hraber, PhD4, Laura Brassard3, Corinne Luedemann3, John-Paul Todd5, Alan Dodson6, Ling Shen3, Adam Buzby3, James Whitney, PhD3, Bette Korber, PhD4, Gary Nabel, MD, PhD7, Mascola John, M.D.5 and Norman Letvin3, (1)Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, (2)Vaccine Research Center, Besthesda, MD, (3)Beth Israel Deaconess Medical Center, Boston, MA, (4)Los Alamos National Laboratory, Los Alamos, NM, (5)Vaccine Research Center, Bethesda, MD, (6)Bioqual, Rockville, MD, (7)National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD

    Disclosures:

    W. Yeh, None

    S. Rao, None

    S. Y. Lim, None

    J. Zhang, None

    P. Hraber, None

    L. Brassard, None

    C. Luedemann, None

    J. P. Todd, None

    A. Dodson, None

    L. Shen, None

    A. Buzby, None

    J. Whitney, None

    B. Korber, None

    G. Nabel, None

    M. John, None

    N. Letvin, None

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