HIV Research Today is a free monthly online journal that collates and summarizes the latest research about HIV, including details on human immunodeficiency virus, testing, treatment, prevention, vaccines, aids.

Neutralizing antibody responses drive the evolution of human immunodeficiency virus type 1 envelope during recent HIV infection.

Frost SD, Wrin T, Smith DM, Kosakovsky Pond SL, Liu Y, Paxinos E, Chappey C, Galovich J, Beauchaine J, Petropoulos CJ, Little SJ, Richman DD

Department of Pathology, University of California at San Diego, La Jolla, CA 92093-0679, USA. sdfrost@ucsd.edu

HIV type 1 (HIV-1) can rapidly escape from neutralizing antibody responses. The genetic basis of this escape in vivo is poorly understood. We compared the pattern of evolution of the HIV-1 env gene between individuals with recent HIV infection whose virus exhibited either a low or a high rate of escape from neutralizing antibody responses. We demonstrate that the rate of viral escape at a phenotypic level is highly variable among individuals, and is strongly correlated with the rate of amino acid substitutions. We show that dramatic escape from neutralizing antibodies can occur in the relative absence of changes in glycosylation or insertions and deletions ("indels") in the envelope; conversely, changes in glycosylation and indels occur even in the absence of neutralizing antibody responses. Comparison of our data with the predictions of a mathematical model support a mechanism in which escape from neutralizing antibodies occurs via many amino acid substitutions, with low cross-neutralization between closely related viral strains. Our results suggest that autologous neutralizing antibody responses may play a pivotal role in the diversification of HIV-1 envelope during the early stages of infection.

Published 21 December 2005 in Proc Natl Acad Sci U S A, 102(51): 18514-9.
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