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

被引:1499
作者
Keele, Brandon F. [1 ]
Giorgi, Elena E. [3 ,4 ]
Salazar-Gonzalez, Jesus F. [1 ]
Decker, Julie M. [1 ]
Pham, Kimmy T. [1 ]
Salazar, Maria G. [1 ]
Sun, Chuanxi [1 ]
Grayson, Truman [1 ]
Wang, Shuyi [1 ]
Li, Hui [1 ]
Wei, Xiping [1 ]
Jiang, Chunlai [5 ]
Kirchherr, Jennifer L. [5 ]
Gao, Feng [5 ]
Anderson, Jeffery A. [7 ]
Ping, Li-Hua
Swanstrom, Ronald [8 ]
Tomaras, Georgia D. [6 ]
Blattner, William A. [9 ]
Goepfert, Paul A. [1 ]
Kilby, J. Michael [1 ]
Saag, Michlael S. [1 ]
Delwart, Eric L. [10 ,11 ]
Busch, Michael P. [10 ,11 ]
Cohen, Myron S. [7 ]
Montefiori, David C. [6 ]
Haynes, Barton F. [5 ]
Gaschen, Brian [3 ]
Athreya, Gayathri S. [3 ]
Lee, Ha Y. [12 ]
Wood, Natasha [13 ]
Seoighe, Cathal [13 ]
Perelson, Alan S. [3 ]
Bhattacharya, Tanmoy [3 ,14 ]
Korber, Bette T. [3 ,14 ]
Hahn, Beatrice H. [1 ,2 ]
Shaw, George M. [1 ,2 ]
机构
[1] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35223 USA
[2] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35223 USA
[3] Los Alamos Natl Lab, Los Alamos, NM 87545 USA
[4] Univ Massachusetts, Dept Math & Stat, Amherst, MA 01002 USA
[5] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA
[6] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA
[7] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA
[8] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA
[9] Univ Maryland, Dept Epidemiol, College Pk, MD 20742 USA
[10] Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94118 USA
[11] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94118 USA
[12] Univ Rochester, Dept Biostat & Computat Biol, Rochester, NY 14642 USA
[13] Univ Cape Town, Inst Infectious Dis & Mol Med, ZA-7701 Rondebosch, South Africa
[14] Santa Fe Inst, Santa Fe, NM 87501 USA
关键词
HIV-1; vaccines; transmitted HIV-1 envelope; viral evolution; virus transmission;
D O I
10.1073/pnas.0802203105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:7552 / 7557
页数:6
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