AEGiS-14IAC: Acute cytotoxic T-lymphocyte escape is a hallmark of simian immunodeficiency virus infection.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Acute cytotoxic T-lymphocyte escape is a hallmark of simian immunodeficiency virus infection.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. TuOrA1179)

OConnor DH, Allen TM, Vogel TU, Jing P, DeSouza IP, Dodds EJ, Yamamoto H, Dunphy EJ, Mothe BR, Hughes AL, Watkins DI
University of Wisconsin at Madison, Madison, United States

BACKGROUND: Cytotoxic T-lymphocyte (CTL) responses may be important in containing human immunodeficiency virus (HIV) replication. Evidence suggests that CTL-resistant viral variants are selected for throughout infection. There are, however, only two examples of HIV escape from strong acute phase CTL responses. Difficulties in studying acute HIV infection can be largely overcome by modeling virus:host interactions in the SIV-infected rhesus macaque.

METHODS: We sequenced 21 complete SIVmac239 genomes at four weeks post-infection and identified regions of the virus evolving under CTL-mediated selective pressure.

RESULTS: Here we show that viruses from 19 of the 21 animals escaped from at least one CTL response during acute infection. This comprehensive analysis identified 7 acute phase CTL responses that select for viral escape variants, including the previously described Mamu-A*01-restricted Tat28-35SL8 response. We are currently extending these findings by sequencing the viruses from this 21-macaque cohort during late-stage infection and by performing high-resolution MHC class I typing on these animals.

CONCLUSIONS: Our results suggest that CTL selection of escape variants is a hallmark of acute SIV infection and that CTL escape may partially explain lentiviral persistence. Moreover, this comprehensive analysis reveals that CTL-mediated selection is the major factor influencing viral diversification during early infection. This finding suggests that unremitting CTL escape may be responsible for the enormous diversity observed among circulating HIV strains.

Keywords: AEGIS, SIV, T-Lymphocytes, Cytotoxic, Macaca mulatta, HIV, HIV Antigens, HIV Infections, Virus Replication, Animal, Human, immunology, virology

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