12th International AIDS Conference Geneva, Switzerland - June 28-July 3, 1998

Int Conf AIDS 1998 Jun 28-Jul 3; 12:20 (abstract no. 11190)

Meyerhans A, Kils-Huetten L, Plikat U
Dept. Virology, University Freiburg, Germany.

OBJECTIVES: To elucidate the driving forces of HIV-1 evolution in vivo.

DESIGN: Longitudinal and cross-sectional comparison of virological and immunological parameters of the index patients with other infected persons and uninfected individuals.

MATERIALS AND METHODS: Intra- and interpatient HIV-1 sequences coding for Gag, Env, and Nef as well as HLA class I and II sequences were obtained from the database. Phylogenetic relationships of aligned sequences were established by split decomposition analysis. The number of synonymous (s) and non synonymous (ns) substitutions, and transitions (ts) and transversions (tv) were counted. The deviation from expected values was evaluated by the chi 2-test.

RESULTS: The phylogeny-based sequence analysis used properly detects positive selection in the antigen presenting segments of HLA proteins. However, for HIV-1 sequences derived from individual patients, either no significant differences were found between the expected and observed number of s/ns substitutions, or s substitutions dominated particularly in the gag region.

CONCLUSIONS: It appears that genetic drift and negative selection are the dominant factors in HIV-1 quasispecies evolution in vivo. Although selection by the immune system may occur, it seems to be an infrequent event.

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