High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men

被引：209

作者：

Li, Hui ^{[1
]}

Bar, Katharine J. ^{[1
]}

Wang, Shuyi ^{[1
]}

Decker, Julie M. ^{[1
]}

Chen, Yalu ^{[1
]}

Sun, Chuanxi ^{[1
]}

Salazar-Gonzalez, Jesus F. ^{[1
]}

Salazar, Maria G. ^{[1
]}

Learn, Gerald H. ^{[1
]}

Morgan, Charity J. ^{[2
]}

Schumacher, Joseph E. ^{[1
]}

Hraber, Peter ^{[3
]}

Giorgi, Elena E. ^{[3
,4
]}

Bhattacharya, Tanmoy ^{[3
,5
]}

Korber, Bette T. ^{[3
,5
]}

Perelson, Alan S. ^{[3
]}

Eron, Joseph J. ^{[6
]}

Cohen, Myron S. ^{[6
]}

Hicks, Charles B. ^{[7
]}

Haynes, Barton F. ^{[7
]}

Markowitz, Martin ^{[8
,9
]}

Keele, Brandon F. ^{[10
]}

Hahn, Beatrice H. ^{[1
,11
]}

Shaw, George M. ^{[1
,11
]}

机构：

[1] Univ Alabama, Dept Med, Birmingham, AL 35294 USA

[2] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA

[3] Los Alamos Natl Lab, Los Alamos, NM USA

[4] Univ Massachusetts, Dept Math & Stat, Amherst, MA 01003 USA

[5] Santa Fe Inst, Santa Fe, NM 87501 USA

[6] Univ N Carolina, Dept Med, Chapel Hill, NC USA

[7] Duke Univ, Dept Med, Durham, NC USA

[8] Aaron Diamond AIDS Res Ctr, New York, NY USA

[9] Rockefeller Univ, New York, NY 10021 USA

[10] NCI, SAIC Frederick, Frederick, MD 21701 USA

[11] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA

来源：

PLOS PATHOGENS | 2010年 / 6卷 / 05期

基金：

比尔及梅琳达.盖茨基金会; 美国国家卫生研究院;

关键词：

HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1; INFECTION; SELECTIVE TRANSMISSION; IN-VIVO; RECOMBINATION; CELLS; DYNAMICS; DIVERSITY; VARIANTS; PREVENT;

D O I：

10.1371/journal.ppat.1000890

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Elucidating virus-host interactions responsible for HIV-1 transmission is important for advancing HIV-1 prevention strategies. To this end, single genome amplification (SGA) and sequencing of HIV-1 within the context of a model of random virus evolution has made possible for the first time an unambiguous identification of transmitted/founder viruses and a precise estimation of their numbers. Here, we applied this approach to HIV-1 env analyses in a cohort of acutely infected men who have sex with men (MSM) and found that a high proportion (10 of 28; 36%) had been productively infected by more than one virus. In subjects with multivariant transmission, the minimum number of transmitted viruses ranged from 2 to 10 with viral recombination leading to rapid and extensive genetic shuffling among virus lineages. A combined analysis of these results, together with recently published findings based on identical SGA methods in largely heterosexual (HSX) cohorts, revealed a significantly higher frequency of multivariant transmission in MSM than in HSX [19 of 50 subjects (38%) versus 34 of 175 subjects (19%); Fisher's exact p = 0.008]. To further evaluate the SGA strategy for identifying transmitted/founder viruses, we analyzed 239 overlapping 5' and 3' half genome or env-only sequences from plasma viral RNA (vRNA) and blood mononuclear cell DNA in an MSM subject who had a particularly well-documented virus exposure history 3 -6 days before symptom onset and 14-17 days before peak plasma viremia (47,600,000 vRNA molecules/ml). All 239 sequences coalesced to a single transmitted/ founder virus genome in a time frame consistent with the clinical history, and a molecular clone of this genome encoded replication competent virus in accord with model predictions. Higher multiplicity of HIV-1 infection in MSM compared with HSX is consistent with the demonstrably higher epidemiological risk of virus acquisition in MSM and could indicate a greater challenge for HIV-1 vaccines than previously recognized.

引用

页码：1 / 17

页数：17

共 60 条

[21] Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1 [J].

Keele, Brandon F. ;

Li, Hui ;

Learn, Gerald H. ;

Hraber, Peter ;

Giorgi, Elena E. ;

Grayson, Truman ;

Sun, Chuanxi ;

Chen, Yalu ;

Yeh, Wendy W. ;

Letvin, Norman L. ;

Mascola, John R. ;

Nabel, Gary J. ;

Haynes, Barton F. ;

Bhattacharya, Tanmoy ;

Perelson, Alan S. ;

Korber, Bette T. ;

Hahn, Beatrice H. ;

Shaw, George M. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2009, 206 (05) :1117-1134

[22] Virus population homogenization following acute human immunodeficiency virus type 1 infection [J].

Learn, GH ;

Muthui, D ;

Brodie, SJ ;

Zhu, TF ;

Diem, K ;

Mullins, JI ;

Corey, L .

JOURNAL OF VIROLOGY, 2002, 76 (23) :11953-11959

[23] Modeling sequence evolution in acute HIV-1 infection [J].

Lee, Ha Youn ;

Giorgi, Elena E. ;

Keele, Brandon F. ;

Gaschen, Brian ;

Athreya, Gayathri S. ;

Salazar-Gonzalez, Jesus F. ;

Pham, Kimmy T. ;

Goepfert, Paula A. ;

Kilby, J. Michael ;

Saag, Michael S. ;

Delwart, Eric L. ;

Busch, Michael P. ;

Hahn, Beatrice H. ;

Shaw, George M. ;

Korber, Bette T. ;

Bhattacharya, Tanmoy ;

Perelson, Alan S. .

JOURNAL OF THEORETICAL BIOLOGY, 2009, 261 (02) :341-360

[24] Moving Forward in HIV Vaccine Development [J].

Letvin, Norman L. .

SCIENCE, 2009, 326 (5957) :1196-1198

[25] Dynamics of HIV-1 recombination in its natural target cells [J].

Levy, DN ;

Aldrovandi, GM ;

Kutsch, O ;

Shaw, GM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (12) :4204-4209

[26] Glycerol monolaurate prevents mucosal SIV transmission [J].

Li, Qingsheng ;

Estes, Jacob D. ;

Schlievert, Patrick M. ;

Duan, Lijie ;

Brosnahan, Amanda J. ;

Southern, Peter J. ;

Reilly, Cavan S. ;

Peterson, Marnie L. ;

Schultz-Darken, Nancy ;

Brunner, Kevin G. ;

Nephew, Karla R. ;

Pambuccian, Stefan ;

Lifson, Jeffrey D. ;

Carlis, John V. ;

Haase, Ashley T. .

NATURE, 2009, 458 (7241) :1034-U113

[27] Visualizing Antigen-Specific and Infected Cells in Situ Predicts Outcomes in Early Viral Infection [J].

Li, Qingsheng ;

Skinner, Pamela J. ;

Ha, Sang-Jun ;

Duan, Lijie ;

Mattila, Teresa L. ;

Hage, Aaron ;

White, Cara ;

Barber, Daniel L. ;

O'Mara, Leigh ;

Southern, Peter J. ;

Reilly, Cavan S. ;

Carlis, John V. ;

Miller, Christopher J. ;

Ahmed, Rafi ;

Haase, Ashley T. .

SCIENCE, 2009, 323 (5922) :1726-1729

[28] Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells [J].

Li, QS ;

Duan, LJ ;

Estes, JD ;

Ma, ZM ;

Rourke, T ;

Wang, YC ;

Reilly, C ;

Carlis, J ;

Miller, CJ ;

Haase, AT .

NATURE, 2005, 434 (7037) :1148-1152

[29] Viral dynamics of acute HIV-1 infection [J].

Little, SJ ;

McLean, AR ;

Spina, CA ;

Richman, DD ;

Havlir, DV .

JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 190 (06) :841-850

[30]

Long EM, 2000, NAT MED, V6, P71

← 1 2 3 4 5 6 →