Alexandre, Kabamba BGray, ESPantophlet, RMoore, PLMcMahon, JBChakauya, EO'Keefe, BRChikwamba, Rachel KMorris, L2011-09-302011-09-302011-09Alexandre, KB, Gray, ES, Pantophlet, R et al. 2011. Binding of the mannose-specific lectin, Griffithsin, to HIV-1 gp120 exposes the CD4-binding site. Journal of Virology, Vol 85(17), pp 9039–90500022-538Xhttp://hdl.handle.net/10204/5190Copyright: 2011 American Society for MicrobiologyThe glycans on HIV-1 gp120 play an important role in shielding neutralization-sensitive epitopes from antibody recognition. They also serve as targets for lectins that bind mannose-rich glycans. In this study, the authors investigated the interaction of the lectin griffithsin (GRFT) with HIV-1 gp120 and its effects on exposure of the CD4-binding site (CD4bs). They found that GRFT enhanced the binding of HIV-1 to plates coated with anti-CD4bs antibodies b12 and b6 or the CD4 receptor mimetic CD4-IgG2. The average enhancement of b12 or b6 binding was higher for subtype B viruses than for subtype C, while for CD4-IgG2, it was similar for both subtypes, although lower than observed with antibodies. This GRFT-mediated enhancement of HIV-1 binding to b12 was reflected in synergistic neutralization for 2 of the 4 viruses tested. The glycan at position 386, which shields the CD4bs, was involved in both GRFT-mediated enhancement of binding and neutralization synergism between GRFT and b12. Although GRFT enhanced CD4bs exposure, it simultaneously inhibited ligand binding to the coreceptor binding site, suggesting that GRFT-dependent enhancement and neutralization utilize independent mechanisms. This study shows for the first time that GRFT interaction with gp120 exposes the CD4bs through binding the glycan at position 386, which may have implications for how to access this conserved siteenHIV-1 glycansGriffithsin lectinCD4-binding sitesHIV-1VirologyMannose-specific lectinMicrobiologyBinding of the mannose-specific lectin, Griffithsin, to HIV-1 gp120 exposes the CD4-binding siteArticleAlexandre, K. B., Gray, E., Pantophlet, R., Moore, P., McMahon, J., Chakauya, E., ... Morris, L. (2011). Binding of the mannose-specific lectin, Griffithsin, to HIV-1 gp120 exposes the CD4-binding site. http://hdl.handle.net/10204/5190Alexandre, Kabamba B, ES Gray, R Pantophlet, PL Moore, JB McMahon, E Chakauya, BR O'Keefe, Rachel K Chikwamba, and L Morris "Binding of the mannose-specific lectin, Griffithsin, to HIV-1 gp120 exposes the CD4-binding site." (2011) http://hdl.handle.net/10204/5190Alexandre KB, Gray E, Pantophlet R, Moore P, McMahon J, Chakauya E, et al. Binding of the mannose-specific lectin, Griffithsin, to HIV-1 gp120 exposes the CD4-binding site. 2011; http://hdl.handle.net/10204/5190.TY - Article AU - Alexandre, Kabamba B AU - Gray, ES AU - Pantophlet, R AU - Moore, PL AU - McMahon, JB AU - Chakauya, E AU - O'Keefe, BR AU - Chikwamba, Rachel K AU - Morris, L AB - The glycans on HIV-1 gp120 play an important role in shielding neutralization-sensitive epitopes from antibody recognition. They also serve as targets for lectins that bind mannose-rich glycans. In this study, the authors investigated the interaction of the lectin griffithsin (GRFT) with HIV-1 gp120 and its effects on exposure of the CD4-binding site (CD4bs). They found that GRFT enhanced the binding of HIV-1 to plates coated with anti-CD4bs antibodies b12 and b6 or the CD4 receptor mimetic CD4-IgG2. The average enhancement of b12 or b6 binding was higher for subtype B viruses than for subtype C, while for CD4-IgG2, it was similar for both subtypes, although lower than observed with antibodies. This GRFT-mediated enhancement of HIV-1 binding to b12 was reflected in synergistic neutralization for 2 of the 4 viruses tested. The glycan at position 386, which shields the CD4bs, was involved in both GRFT-mediated enhancement of binding and neutralization synergism between GRFT and b12. Although GRFT enhanced CD4bs exposure, it simultaneously inhibited ligand binding to the coreceptor binding site, suggesting that GRFT-dependent enhancement and neutralization utilize independent mechanisms. This study shows for the first time that GRFT interaction with gp120 exposes the CD4bs through binding the glycan at position 386, which may have implications for how to access this conserved site DA - 2011-09 DB - ResearchSpace DP - CSIR KW - HIV-1 glycans KW - Griffithsin lectin KW - CD4-binding sites KW - HIV-1 KW - Virology KW - Mannose-specific lectin KW - Microbiology LK - https://researchspace.csir.co.za PY - 2011 SM - 0022-538X T1 - Binding of the mannose-specific lectin, Griffithsin, to HIV-1 gp120 exposes the CD4-binding site TI - Binding of the mannose-specific lectin, Griffithsin, to HIV-1 gp120 exposes the CD4-binding site UR - http://hdl.handle.net/10204/5190 ER -