Mannose-rich glycosylation patterns on HIV-1 subtype C gp120 and sensitivity to the lectins, Griffithsin, Cyanovirin-N and Scytovirin

作者：Alexandre Kabamba B; Gray Elin S; Lambson Bronwen E; Moore Penny L; Choge Isaac A; Mlisana Koleka; Karim Salim S Abdool; McMahon James; O'Keefe Barry; Chikwamba Rachel; Morris Lynn^*

来源：Virology, 2010, 402(1): 187-196.

DOI：10.1016/j.virol.2010.03.021

• Griffithsin
• Cyanovirin-N
• Scytovirin
• Lectins
• HIV-1 subtype C
• Microbicides
• 2G12 monoclonal antibody

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 IC(50) 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.

• 出版日期2010-6-20