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

Publication ,  Journal Article
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; Gao, F ...
Published in: Proc Natl Acad Sci U S A
May 27, 2008

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.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

May 27, 2008

Volume

105

Issue

21

Start / End Page

7552 / 7557

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Sequence Analysis, RNA
  • Receptors, CCR5
  • RNA, Viral
  • Phylogeny
  • Mutation
  • Molecular Sequence Data
  • Models, Biological
  • Humans
  • HIV-1
 

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Keele, B. F., Giorgi, E. E., Salazar-Gonzalez, J. F., Decker, J. M., Pham, K. T., Salazar, M. G., … Shaw, G. M. (2008). Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A, 105(21), 7552–7557. https://doi.org/10.1073/pnas.0802203105
Keele, Brandon F., Elena E. Giorgi, Jesus F. Salazar-Gonzalez, Julie M. Decker, Kimmy T. Pham, Maria G. Salazar, Chuanxi Sun, et al. “Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection.Proc Natl Acad Sci U S A 105, no. 21 (May 27, 2008): 7552–57. https://doi.org/10.1073/pnas.0802203105.
Keele BF, Giorgi EE, Salazar-Gonzalez JF, Decker JM, Pham KT, Salazar MG, et al. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A. 2008 May 27;105(21):7552–7.
Keele, Brandon F., et al. “Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection.Proc Natl Acad Sci U S A, vol. 105, no. 21, May 2008, pp. 7552–57. Pubmed, doi:10.1073/pnas.0802203105.
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. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A. 2008 May 27;105(21):7552–7557.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

May 27, 2008

Volume

105

Issue

21

Start / End Page

7552 / 7557

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Sequence Analysis, RNA
  • Receptors, CCR5
  • RNA, Viral
  • Phylogeny
  • Mutation
  • Molecular Sequence Data
  • Models, Biological
  • Humans
  • HIV-1