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

[1] Temporal and anatomic relationship between virus replication and cytokine gene expression after vaginal simian immunodeficiency virus infection [J].

Abel, K ;

Rocke, DM ;

Chohan, B ;

Fritts, L ;

Miller, CJ .

JOURNAL OF VIROLOGY, 2005, 79 (19) :12164-12172

[2] Donor and Recipient Envs from Heterosexual Human Immunodeficiency Virus Subtype C Transmission Pairs Require High Receptor Levels for Entry [J].

Alexander, Melissa ;

Lynch, Rebecca ;

Mulenga, Joseph ;

Allen, Susan ;

Derdeyn, Cynthia A. ;

Hunter, Eric .

JOURNAL OF VIROLOGY, 2010, 84 (08) :4100-4104

[3] Within-host and between-host evolutionary rates across the HIV-1 genome [J].

Alizon, Samuel ;

Fraser, Christophe .

RETROVIROLOGY, 2013, 10

[4]

Baalwa J., 2012, Virology

[5]

Boeras D I., 2011, Proc. Natl Acad. Sci

[6] Selection bias at the heterosexual HIV-1 transmission bottleneck [J].

Carlson, Jonathan M. ;

Schaefer, Malinda ;

Monaco, Daniela C. ;

Batorsky, Rebecca ;

Claiborne, Daniel T. ;

Prince, Jessica ;

Deymier, Martin J. ;

Ende, Zachary S. ;

Klatt, Nichole R. ;

DeZiel, Charles E. ;

Lin, Tien-Ho ;

Peng, Jian ;

Seese, Aaron M. ;

Shapiro, Roger ;

Frater, John ;

Ndung'u, Thumbi ;

Tang, Jianming ;

Goepfert, Paul ;

Gilmour, Jill ;

Price, Matt A. ;

Kilembe, William ;

Heckerman, David ;

Goulder, Philip J. R. ;

Allen, Todd M. ;

Allen, Susan ;

Hunter, Eric .

SCIENCE, 2014, 345 (6193)

[7]

Cavrois M, 2013, J VIROL, V11

[8] Selection for human immunodeficiency virus type I envelope glycosylation variants with shorter V1-V2 loop sequences occurs during transmission of certain genetic subtypes and may impact viral RNA levels [J].

Chohan, B ;

Lang, D ;

Sagar, M ;

Korber, B ;

Lavreys, L ;

Richardson, B ;

Overbaugh, J .

JOURNAL OF VIROLOGY, 2005, 79 (10) :6528-6531

[9] A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses [J].

Claiborne, Daniel T. ;

Prince, Jessica L. ;

Hunter, Eric .

JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2014, (90)

[10]

Claiborne DT, 2015, PROCEEDINGS OF THE N

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