Determinants in V2C2 region of HIV-1 clade C primary envelopes conferred altered neutralization susceptibilities to IgG1b12 and PG9 monoclonal antibodies in a context-dependent manner

被引:1
|
作者
Patil, Shilpa [1 ]
Choudhary, Ipsita [2 ]
Chaudhary, Nakul K. [1 ]
Ringe, Rajesh [2 ]
Bansal, Manish [1 ]
Shukla, Brihaspati Narayan [1 ]
Boliar, Saikat [1 ]
Chakrabarti, Bimal K. [1 ]
Bhattacharya, Jayanta [1 ]
机构
[1] Translat Hlth Sci & Technol Inst, THSTI IAVI HIV Vaccine Design Program, HIV Vaccine Translat Res Lab, Gurgaon 122016, Haryana, India
[2] Natl AIDS Res Inst, Pune, Maharashtra, India
关键词
HIV-1; Cade C; Envelope; Neutralizing antibody; CD4bs; IgG1b12; VRC01; PG9; PG16; IMMUNODEFICIENCY-VIRUS TYPE-1; CD4; BINDING-SITE; GLYCOPROTEIN GP120; ENV CLONES; SUBTYPE-B; INFECTION; LOOP; RESISTANCE; EVOLUTION; BROAD;
D O I
10.1016/j.virol.2014.06.018
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
In the present study by examining pseudoviruses expressing patient chimeric envelopes (Envs) made between an IgG1b12 (b12)-sensitive (2-5.J3) and a b12-resistant (4.J22) HIV-1 clade C envelope, we identified determinants in the V2C2 region that governed susceptibility to b12 monoclonal antibody, but not to other CD4 binding site antibodies. Interestingly, when the V2C2 sequence of the 2-5.J3 Env was transferred to other b12-resistant primary clade C Envs, their susceptibility to b12 varied, indicating that this effect was context dependent. In addition, we identified determinants within the V2 region in the b12-resistant envelope that significantly modulated the neutralization of Env-pseudotyped viruses to PG9/PG16 MAbs. The enhanced neutralization susceptibilities of Envs to b12 and PG9 MAbs were correlated with increased exposure of their corresponding epitopes highlighting vulnerabilities in the V2C2 region that altered Env conformation necessary for the efficient accessibility of b12 and PG9 antibodies. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:266 / 272
页数:7
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