期刊
VIROLOGY
卷 402, 期 1, 页码 187-196出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2010.03.021
关键词
Griffithsin; Cyanovirin-N; Scytovirin; Lectins; HIV-1 subtype C; Microbicides; 2G12 monoclonal antibody
类别
资金
- NEPAD
- South African AIDS Vaccine Initiative (SAAVI)
- CAPRISA
- National Institute of Allergy and infectious Disease (NIAID), National Institutes of Health (NIH)
- National Research Foundation
- Fogarty International Center
- LifeLab, a biotechnology centre of the South African Government Department of Science and Technology
- NIH, National Cancer Institute, Center for Cancer Research
Griffithsin (GRFT), Cyanovirin-N (CV-N) and Scytovirin (SVN) are lectins that inhibit HIV-1 infection by binding to multiple mannose-rich glycans on the HIV-1 envelope glycoproteins (Env). Here we show that these lectins neutralize subtype C primary virus isolates in addition to Env-pseudotyped viruses obtained from plasma and cervical vaginal lavages. Among 15 subtype C pseudoviruses, the median IC50 values were 0.4, 1.8 and 20.1 nM for GRFT, CV-N and SVN, respectively, similar to what was found for subtype B and A. Analysis of Env sequences suggested that concomitant lack of glycans at positions 234 and 295 resulted in natural resistance to these compounds, which was confirmed by site-directed mutagenesis. Furthermore, the binding sites for these lectins overlapped that of the 2G12 monoclonal antibody epitope, which is generally absent on subtype C Env. This data support further research on these lectins as potential microbicides in the context of HIV-1 subtype C infection. (C) 2010 Elsevier Inc. All rights reserved.
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