Mechanisms of HIV-1 subtype C resistance to GRFT, CV-N and SVN

被引：29

作者：

Alexandre, Kabamba B. ^{[1
,2
]}

Moore, Penny L. ^{[1
,2
]}

Nonyane, Molati ^{[1
]}

Gray, Elin S. ^{[1
]}

Ranchobe, Nthabeleng ^{[1
]}

Chakauya, Ereck ^{[3
]}

McMahon, James B. ^{[4
]}

O'Keefe, Barry R. ^{[4
]}

Chikwamba, Rachel ^{[3
]}

Morris, Lynn ^{[1
,2
]}

机构：

[1] Natl Inst Communicable Dis, Ctr HIV & STIs, ZA-2131 Johannesburg, South Africa

[2] Univ Witwatersrand, Johannesburg, South Africa

[3] CSIR, ZA-0001 Pretoria, South Africa

[4] NCI Frederick, Mol Targets Lab, Ctr Canc Res, Frederick, MD USA

来源：

VIROLOGY | 2013年 / 446卷 / 1-2期

基金：

英国惠康基金;

关键词：

Griffithsin; Cyanovirin-N; Scytovirin; HIV subtype C; Resistance; Entry inhibitor; Glycans; Single genome amplification; Microbicide; HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN GP120; ENTRY INHIBITOR GRIFFITHSIN; CYANOVIRIN-N; ANTIBODY NEUTRALIZATION; CARBOHYDRATE-BINDING; LINKED GLYCOSYLATION; INACTIVATING PROTEIN; TYPE-1; STRAINS; PLANT-LECTINS;

D O I：

10.1016/j.virol.2013.07.019

中图分类号：

Q93 [微生物学];

学科分类号：

071005 [微生物学];

摘要：

We examined the ability of HIV-1 subtype C to develop resistance to the inhibitory lectins, griffithsin (GRFT), cyanovirin-N (CV-N) and scytovirin (SVN), which bind multiple mannose-rich glycans on gp120. Four primary HIV-1 strains cultured under escalating concentrations of these lectins became increasingly resistant tolerating 2 to 12 times their 50% inhibitory concentrations. Sequence analysis of gp120 showed that most had deletions of 1 to 5 mannose-rich glycans. Glycosylation sites at positions 230, 234, 241, 289 located in the C2 region and 339,392 and 448 in the C3-C4 region were affected. Furthermore, deletions and insertions of up to 5 amino acids in the V4 region were observed in 3 of the 4 isolates. These data suggest that loss of glycosylation sites on gp120 as well as rearrangement of glycans in V4 are mechanisms involved in HIV-1 subtype C escape from GRFT, CV-N and SVN. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：66 / 76

页数：11

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