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

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 b...

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Bibliographic Details
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
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Summary: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.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2013.07.019