Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection.

Published

Journal Article

The precise identification of the HIV-1 envelope glycoprotein (Env) responsible for productive clinical infection could be instrumental in elucidating the molecular basis of HIV-1 transmission and in designing effective vaccines. Here, we developed a mathematical model of random viral evolution and, together with phylogenetic tree construction, used it to analyze 3,449 complete env sequences derived by single genome amplification from 102 subjects with acute HIV-1 (clade B) infection. Viral env genes evolving from individual transmitted or founder viruses generally exhibited a Poisson distribution of mutations and star-like phylogeny, which coalesced to an inferred consensus sequence at or near the estimated time of virus transmission. Overall, 78 of 102 subjects had evidence of productive clinical infection by a single virus, and 24 others had evidence of productive clinical infection by a minimum of two to five viruses. Phenotypic analysis of transmitted or early founder Envs revealed a consistent pattern of CCR5 dependence, masking of coreceptor binding regions, and equivalent or modestly enhanced resistance to the fusion inhibitor T1249 and broadly neutralizing antibodies compared with Envs from chronically infected subjects. Low multiplicity infection and limited viral evolution preceding peak viremia suggest a finite window of potential vulnerability of HIV-1 to vaccine-elicited immune responses, although phenotypic properties of transmitted Envs pose a formidable defense.

Full Text

Duke Authors

Cited Authors

  • Keele, BF; Giorgi, EE; Salazar-Gonzalez, JF; Decker, JM; Pham, KT; Salazar, MG; Sun, C; Grayson, T; Wang, S; Li, H; Wei, X; Jiang, C; Kirchherr, JL; Gao, F; Anderson, JA; Ping, L-H; Swanstrom, R; Tomaras, GD; Blattner, WA; Goepfert, PA; Kilby, JM; Saag, MS; Delwart, EL; Busch, MP; Cohen, MS; Montefiori, DC; Haynes, BF; Gaschen, B; Athreya, GS; Lee, HY; Wood, N; Seoighe, C; Perelson, AS; Bhattacharya, T; Korber, BT; Hahn, BH; Shaw, GM

Published Date

  • May 19, 2008

Published In

Volume / Issue

  • 105 / 21

Start / End Page

  • 7552 - 7557

PubMed ID

  • 18490657

Pubmed Central ID

  • 18490657

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0802203105

Language

  • eng