Highly complex neutralization determinants on a monophyletic lineage of newly transmitted subtype C HIV-1 Env clones from India

被引：74

作者：

Kulkarni, Smita S. ^{[2
]}

Lapedes, Alan ^{[3
]}

Tang, Haili ^{[1
]}

Gnanakaran, S. ^{[3
]}

Daniels, Marcus G. ^{[3
]}

Zhang, Ming ^{[3
]}

Bhattacharya, Tanmoy ^{[3
]}

Li, Ming ^{[1
]}

Polonis, Victoria R. ^{[4
,5
]}

McCutchan, Francine E. ^{[4
,5
]}

Morris, Lynn ^{[6
]}

Ellenberger, Dennis ^{[7
]}

Butera, Salvatore T. ^{[7
]}

Bollinger, Robert C. ^{[8
]}

Korber, Bette T. ^{[3
]}

Paranjape, Ramesh S. ^{[2
]}

Montefiori, David C. ^{[1
]}

机构：

[1] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA

[2] Natl AIDS Res Inst, Pune, Maharashtra, India

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

[4] Walter Reed Army Inst Res, Rockville, MD 20850 USA

[5] Henry M Jackson Fdn, Rockville, MD 20850 USA

[6] Natl Inst Communicable Dis, Johannesburg, South Africa

[7] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA

[8] Johns Hopkins Sch Med, Dept Med, Div Infect Dis, Baltimore, MD USA

来源：

VIROLOGY | 2009年 / 385卷 / 02期

基金：

美国国家卫生研究院;

关键词：

HIV-1; Neutralizing antibodies; Envelope glycoproteins; Genetic signatures; Heatmap; HUMAN-IMMUNODEFICIENCY-VIRUS; GP120 ENVELOPE GLYCOPROTEIN; PROXIMAL EXTERNAL REGION; CELL-SURFACE EXPRESSION; CORECEPTOR BINDING-SITE; GP41 CYTOPLASMIC TAIL; TYPE-1; ENVELOPE; ANTIBODY NEUTRALIZATION; MONOCLONAL-ANTIBODIES; GENETIC DIVERSITY;

D O I：

10.1016/j.virol.2008.12.032

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Little is known about the neutralization properties of HIV-1 in India to optimally design and test vaccines. For this reason, a functional Env clone was obtained from each of ten newly acquired, heterosexually transmitted HIV-1 infections in Pune, Maharashtra, These clones formed a phylogenetically distinct genetic lineage within subtype C. As Env-pseudotyped Viruses the clones were mostly resistant to IgG1b12, 2G12 and 2F5 but all were sensitive to 4E10. When compared to a large multi-subtype panel of Env-pseudotyped viruses (subtypes B, C and CRF02_AG) in neutralization assays with a multi-subtype panel of HIV-1-positive plasma samples, the Indian Envs were remarkably complex. With the exception of the Indian Envs, results of a hierarchical clustering analysis showed a strong subtype association with the patterns of neutralization susceptibility. From these patterns we were able to identify 19 neutralization cluster-associated amino acid signatures in gp120 and 14 signatures in the ectodomain and cytoplasmic tail of gp41. We conclude that newly transmitted Indian Envs are antigenically complex in spite of close genetic similarity. Delineation of neutralization-associated amino acid signatures provides a deeper understanding of the antigenic structure of HIV-1 Env. (c) 2008 Elsevier Inc. All rights reserved.

引用

页码：505 / 520

页数：16

共 111 条

[1]

AGNIHOTRI K, 2004, AIDS RES HUM RETROV, V20, P889

[2] Molecular analysis of gp41 sequences of HIV type 1 subtype C from India [J].