Heterosexual Transmission of Subtype C HIV-1 Selects Consensus-Like Variants without Increased Replicative Capacity or Interferon-α Resistance

被引：72

作者：

Deymier, Martin J. ^{[1
]}

Ende, Zachary ^{[1
]}

Fenton-May, Angharad E. ^{[2
]}

Dilernia, Dario A. ^{[1
]}

Kilembe, William ^{[3
]}

Allen, Susan A. ^{[4
]}

Borrow, Persephone ^{[2
]}

Hunter, Eric ^{[1
,4
]}

机构：

[1] Emory Univ, Emory Vaccine Ctr, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA

[2] Univ Oxford, Nuffield Dept Med, Oxford, England

[3] Zambia Emory HIV Res Project, Lusaka, Zambia

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

来源：

PLOS PATHOGENS | 2015年 / 11卷 / 09期

基金：

美国国家卫生研究院;

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; INFECTIOUS MOLECULAR CLONES; DISEASE PROGRESSION; CCR5; UTILIZATION; TRANSMITTED/FOUNDER; GLYCOSYLATION; LENGTH; NEUTRALIZATION; IDENTIFICATION; AMPLIFICATION;

D O I：

10.1371/journal.ppat.1005154

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Heterosexual transmission of HIV-1 is characterized by a genetic bottleneck that selects a single viral variant, the transmitted/founder (TF), during most transmission events. To assess viral characteristics influencing HIV-1 transmission, we sequenced 167 near full-length viral genomes and generated 40 infectious molecular clones (IMC) including TF variants and multiple non-transmitted (NT) HIV-1 subtype C variants from six linked heterosexual transmission pairs near the time of transmission. Consensus-like genomes sensitive to donor antibodies were selected for during transmission in these six transmission pairs. However, TF variants did not demonstrate increased viral fitness in terms of particle infectivity or viral replicative capacity in activated peripheral blood mononuclear cells (PBMC) and monocyte-derived dendritic cells (MDDC). In addition, resistance of the TF variant to the antiviral effects of interferon-a (IFN-alpha) was not significantly different from that of non-transmitted variants from the same transmission pair. Thus neither in vitro viral replicative capacity nor IFN-a resistance discriminated the transmission potential of viruses in the quasispecies of these chronically infected individuals. However, our findings support the hypothesis that within-host evolution of HIV-1 in response to adaptive immune responses reduces viral transmission potential.

引用

页数：22

共 54 条

[11] DIVEIN: a web server to analyze phylogenies, sequence divergence, diversity, and informative sites [J].

Deng, Wenjie ;

Maust, Brandon S. ;

Nickle, David C. ;

Learn, Gerald H. ;

Liu, Yi ;

Heath, Laura ;

Pond, Sergei L. Kosakovsky ;

Mullins, James I. .

BIOTECHNIQUES, 2010, 48 (05) :405-408

[12] Envelope-constrained neutralization-sensitive HIV-1 after heterosexual transmission [J].

Derdeyn, CA ;

Decker, JM ;

Bibollet-Ruche, F ;

Mokili, JL ;

Muldoon, M ;

Denham, SA ;

Heil, ML ;

Kasolo, F ;

Musonda, R ;

Hahn, BH ;

Shaw, GM ;

Korber, BT ;

Allen, S ;

Hunter, E .

SCIENCE, 2004, 303 (5666) :2019-2022

[13] Particle infectivity of HIV-1 full-length genome infectious molecular clones in a subtype C heterosexual transmission pair following high fidelity amplification and unbiased cloning [J].

Deymier, Martin J. ;

Claiborne, Daniel T. ;

Ende, Zachary ;

Ratner, Hannah K. ;

Kilembe, William ;

Allen, Susan ;

Hunter, Eric .

VIROLOGY, 2014, 468 :454-461

[14] Multiplexed highly-accurate DNA sequencing of closely-related HIV-1 variants using continuous long reads from single molecule, real-time sequencing [J].

Dilernia, Dario A. ;

Chien, Jung-Ting ;

Monaco, Daniela C. ;

Brown, Michael P. S. ;

Ende, Zachary ;

Deymier, Martin J. ;

Yue, Ling ;

Paxinos, Ellen E. ;

Allen, Susan ;

Tirado-Ramos, Alfredo ;

Hunter, Eric .

NUCLEIC ACIDS RESEARCH, 2015, 43 (20)

[15] Lack of Protection following Passive Transfer of Polyclonal Highly Functional Low-Dose Non-Neutralizing Antibodies [J].

Dugast, Anne-Sophie ;

Chan, Ying ;

Hoffner, Michelle ;

Licht, Anna ;

Nkolola, Joseph ;

Li, Hualin ;

Streeck, Hendrik ;

Suscovich, Todd J. ;

Ghebremichael, Musie ;

Ackerman, Margaret E. ;

Barouch, Dan H. ;

Alter, Galit .

PLOS ONE, 2014, 9 (05)

[16] MUSCLE: multiple sequence alignment with high accuracy and high throughput [J].

Edgar, RC .

NUCLEIC ACIDS RESEARCH, 2004, 32 (05) :1792-1797

[17] INVITRO RESISTANCE TO ZIDOVUDINE AND ALPHA-INTERFERON IN HIV-1 ISOLATES FROM PATIENTS - CORRELATIONS WITH TREATMENT DURATION AND RESPONSE [J].

EDLIN, BR ;

STCLAIR, MH ;

PITHA, PM ;

WHALING, SM ;

KING, DM ;

BITRAN, JD ;

WEINSTEIN, RA .

ANNALS OF INTERNAL MEDICINE, 1992, 117 (06) :457-460

[18] Gene Loss and Adaptation to Hominids Underlie the Ancient Origin of HIV-1 [J].

Etienne, Lucie ;

Hahn, Beatrice H. ;

Sharp, Paul M. ;

Matsen, Frederick A. ;

Emerman, Michael .

CELL HOST & MICROBE, 2013, 14 (01) :85-92

[19] Relative resistance of HIV-1 founder viruses to control by interferon-alpha [J].

Fenton-May, Angharad E. ;

Dibben, Oliver ;

Emmerich, Tanja ;

Ding, Haitao ;

Pfafferott, Katja ;

Aasa-Chapman, Marlen M. ;

Pellegrino, Pierre ;

Williams, Ian ;

Cohen, Myron S. ;

Gao, Feng ;

Shaw, George M. ;

Hahn, Beatrice H. ;

Ochsenbauer, Christina ;

Kappes, John C. ;

Borrow, Persephone .

RETROVIROLOGY, 2013, 10

[20] Sexually-Transmitted/Founder HIV-1 Cannot Be Directly Predicted from Plasma or PBMC-Derived Viral Quasispecies in the Transmitting Partner [J].

Frange, Pierre ;

Meyer, Laurence ;

Jung, Matthieu ;

Goujard, Cecile ;

Zucman, David ;

Abel, Sylvie ;

Hochedez, Patrick ;

Gousset, Marine ;

Gascuel, Olivier ;

Rouzioux, Christine ;

Chaix, Marie-Laure .

PLOS ONE, 2013, 8 (07)

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