Journal
VIROLOGY
Volume 418, Issue 2, Pages 123-132Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2011.07.015
Keywords
HIV-1; Neutralizing antibody; V3 loop; CD4bs; Clade C; Envelope; C4 domain; Recent infection
Categories
Funding
- Department of Biotechnology, Government of India [BT/PR7829/MED/14/1133/2006, BT/PR12853/MED/29/141/2009]
- Collaboration of AIDS Vaccine Discovery (CAVD)
- Vaccine Immune Monitoring Consortium (VIMC) [38619]
- USA National Institutes of Health [AI 36085, HL59725, AI27747]
- Bill and Melinda Gates Foundation
- USA Department of Veterans Affairs
- Council of Scientific and Industrial Research (CSIR)
- University Grants Commission (UGC), Government of India
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Identification of vulnerability in the HIV-1 envelope (Env) will aid in Env-based vaccine design. We recently found an HIV-1 clade C Env clone (4-2.J45) amplified from a recently infected Indian patient showing exceptional neutralization sensitivity to autologous plasma in contrast to other autologous Envs obtained at the same time point. By constructing chimeric Envs and fine mapping between sensitive and resistant Env clones, we found that substitution of highly conserved isoleucine (I) with methionine (M) (ATA to ATG) at position 424 in the C4 domain conferred enhanced neutralization sensitivity of Env-pseudotyped viruses to autologous and heterologous plasma antibodies. When tested against monoclonal antibodies targeting different sites in gp120 and gp41, Envs expressing M424 showed significant sensitivity to anti-V3 monoclonal antibodies and modestly to sCD4 and b12. Substitution of I424M in unrelated Envs also showed similar neutralization phenotype, indicating that M424 in C4 region induces exposure of neutralizing epitopes particularly in CD4 binding sites and V3 loop. (C) 2011 Elsevier Inc. All rights reserved.
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