Mechanisms of HIV-1 subtype C resistance to GRFT, CV-N and SVN

• Published in: Virology (New York, N.Y.) N.Y.), 2013-11, Vol.446 (1), p.66-76
• Main Authors: Alexandre, Kabamba B, Moore, Penny L, Nonyane, Molati, Gray, Elin S, Ranchobe, Nthabeleng, Chakauya, Ereck, McMahon, James B, O’Keefe, Barry R, Chikwamba, Rachel, Morris, Lynn
• Format: Article
• Language: English
• Subjects: Antiviral Agents - pharmacology; Bacterial Proteins - pharmacology; Carrier Proteins - pharmacology; Cell Line; Cyanovirin-N; Drug Resistance, Viral; Drug Tolerance; Entry inhibitor; Glycans; Glycosylation; Griffithsin; HIV Envelope Protein gp120 - genetics; HIV subtype C; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - growth & development; Human immunodeficiency virus 1; Humans; Infectious Disease; Inhibitory Concentration 50; Lectins - pharmacology; Membrane Proteins; Microbial Sensitivity Tests; Microbicide; Mutant Proteins - genetics; Mutation, Missense; Plant Lectins - pharmacology; Resistance; Scytovirin; Sequence Analysis, DNA; Serial Passage; Single genome amplification
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2013.07.019

Abstract We examined the ability of HIV-1 subtype C to develop resistance to the inhibitory lectins, griffithsin (GRFT), cyanovirin-N (CV-N) and scytovirin (SVN), which bind multiple mannose-rich glycans on gp120. Four primary HIV-1 strains cultured under escalating concentrations of these lectins became increasingly resistant tolerating 2 to 12 times their 50% inhibitory concentrations. Sequence analysis of gp120 showed that most had deletions of 1 to 5 mannose-rich glycans. Glycosylation sites at positions 230, 234, 241, 289 located in the C2 region and 339, 392 and 448 in the C3-C4 region were affected. Furthermore, deletions and insertions of up to 5 amino acids in the V4 region were observed in 3 of the 4 isolates. These data suggest that loss of glycosylation sites on gp120 as well as rearrangement of glycans in V4 are mechanisms involved in HIV-1 subtype C escape from GRFT, CV-N and SVN.