title: Neutralizing antibody responses drive the evolution of human immunodeficiency virus type 1 envelope during recent HIV infection.
abstract: 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.
authors.affiliation: Department of Pathology, University of California at San Diego, La Jolla, CA 92093-0679, USA. sdfrost@ucsd.edu
authors.forename: Simon D W
authors.initials: SD
authors.lastname: Frost
authors.forename: Terri
authors.initials: T
authors.lastname: Wrin
authors.forename: Davey M
authors.initials: DM
authors.lastname: Smith
authors.forename: Sergei L
authors.initials: SL
authors.lastname: Kosakovsky Pond
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Ellen
authors.initials: E
authors.lastname: Paxinos
authors.forename: Colombe
authors.initials: C
authors.lastname: Chappey
authors.forename: Justin
authors.initials: J
authors.lastname: Galovich
authors.forename: Jeff
authors.initials: J
authors.lastname: Beauchaine
authors.forename: Christos J
authors.initials: CJ
authors.lastname: Petropoulos
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Little
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Richman
mesh_terms: D000328:Adult; D019143:Evolution, Molecular; D015686:Gene Products, env / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010641:Phenotype; D013997:Time Factors
chemical_list: D015686:Gene Products, env; D015483:HIV Antibodies