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Browsing by Author "Alexandre, Kabamba B."

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    Mannose-rich glycosylation patterns on HIV-1 subtype C gp120 and sensitivity to the lectins, Griffithsin, Cyanovirin-N and Scytovirin.
    (Elsevier., 2010) Alexandre, Kabamba B.; Gray, Elin Solomonovna.; Lambson, Bronwen Elizabeth.; Moore, Penelope L.; Choge, Isaac Ang'Ang'A.; Mlisana, Koleka Patience.; Abdool Karim, Salim Safurdeen.; McMahon, James.; O'Keefe, Barry.; Chikwamba, Rachel.; Morris, Lynn.
    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.