Selection bias at the heterosexual HIV-1 transmission bottleneck

被引：201

作者：

Carlson, Jonathan M. ^{[1
]}

Schaefer, Malinda ^{[2
]}

Monaco, Daniela C. ^{[2
]}

Batorsky, Rebecca ^{[3
]}

Claiborne, Daniel T. ^{[2
]}

Prince, Jessica ^{[2
]}

Deymier, Martin J. ^{[2
]}

Ende, Zachary S. ^{[2
]}

Klatt, Nichole R. ^{[2
]}

DeZiel, Charles E. ^{[1
]}

Lin, Tien-Ho ^{[1
]}

Peng, Jian ^{[1
]}

Seese, Aaron M. ^{[3
]}

Shapiro, Roger ^{[4
]}

Frater, John ^{[5
,6
,7
]}

Ndung'u, Thumbi ^{[3
,8
,9
]}

Tang, Jianming ^{[10
]}

Goepfert, Paul ^{[10
]}

Gilmour, Jill ^{[11
,12
]}

Price, Matt A. ^{[13
,14
]}

Kilembe, William ^{[15
]}

Heckerman, David ^{[16
]}

Goulder, Philip J. R. ^{[8
,17
]}

Allen, Todd M. ^{[3
]}

Allen, Susan ^{[15
,18
,19
]}

Hunter, Eric ^{[2
,15
,18
]}

机构：

[1] Microsoft Res, Redmond, WA 98052 USA

[2] Emory Univ, Yerkes Natl Primate Res Ctr, Emory Vaccine Ctr, Atlanta, GA 30329 USA

[3] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02114 USA

[4] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA

[5] Univ Oxford, Nuffield Dept Clin Med, Oxford OX1 7BN, England

[6] Oxford Biomed Res Ctr, Natl Inst Hlth Res, Oxford OX3 7LE, England

[7] Univ Oxford, Oxford Martin Sch, Oxford OX1 3BD, England

[8] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Durban, South Africa

[9] Max Planck Inst Infekt Biol, D-10117 Berlin, Germany

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

[11] Int AIDS Vaccine Initiat, London SW10 9NH, England

[12] Univ London Imperial Coll Sci Technol & Med, London SW10 9NH, England

[13] Int AIDS Vaccine Initiat, San Francisco, CA 94105 USA

[14] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94105 USA

[15] Zambia Emory HIV Res Project, Rwanda Zambia HIV Res Grp, Lusaka, Zambia

[16] Microsoft Res, Los Angeles, CA USA

[17] Univ Oxford, Dept Paediat, Oxford OX1 3SY, England

[18] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA

[19] Emory Univ, Rollins Sch Publ Hlth, Dept Global Hlth, Atlanta, GA 30322 USA

来源：

SCIENCE | 2014年 / 345卷 / 6193期

基金：

新加坡国家研究基金会;

关键词：

VIRUS TYPE-1 TRANSMISSION; CLASS-I ALLELES; REPLICATION CAPACITY; ESCAPE MUTATIONS; VIRAL-LOAD; SEXUAL TRANSMISSION; DISCORDANT COUPLES; IMMUNE CONTROL; GAG; INFECTION;

D O I：

10.1126/science.1254031

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：

Heterosexual transmission of HIV-1 typically results in one genetic variant establishing systemic infection. We compared, for 137 linked transmission pairs, the amino acid sequences encoded by non-envelope genes of viruses in both partners and demonstrate a selection bias for transmission of residues that are predicted to confer increased in vivo fitness on viruses in the newly infected, immunologically naive recipient. Although tempered by transmission risk factors, such as donor viral load, genital inflammation, and recipient gender, this selection bias provides an overall transmission advantage for viral quasispecies that are dominated by viruses with high in vivo fitness. Thus, preventative or therapeutic approaches that even marginally reduce viral fitness may lower the overall transmission rates and offer long-term benefits even upon successful transmission.

引用

页数：14

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