Specific sequences commonly found in the V3 domain of HIV-1 subtype C isolates affect the overall conformation of native Env and induce a neutralization-resistant phenotype independent of V1/V2 masking

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• 作者：Aidy Salomon ; Chavdar Krachmarov ; Zhong Lai ; William Honnen ; Barry S. Zingman ; Julie Sarlo ; Miroslaw K. Gorny ; Susan Zolla-Pazner ; James E. Robinson ; Abraham Pinter
• 关键词：HIV-1 ; Subtype C ; V3 domain ; Conformational effect ; Epitope masking
• 刊名：Virology
• 出版年：5 January, 2014
• 年：2014
• 卷：448
• 期：Complete
• 页码：363-374
• 全文大小：2335 K

文摘

Primary HIV-1 isolates are relatively resistant to neutralization by antibodies commonly induced after infection or vaccination. This is generally attributed to masking of sensitive epitopes by the V1/V2 domain and/or glycans situated at various positions in Env. Here we identified a novel masking effect mediated by subtype C-specific V3 sequences that contributes to the V1/V2-independent and glycan-independent neutralization resistance of chimeric and primary Envs to antibodies directed against multiple neutralization domains. Positions at several conserved charged and hydrophobic sites in the V3 crown and stem were also shown to affect neutralization phenotype. These results indicated that substitutions typically present in subtype C and related V3 sequences influence the overall conformation of native Env in a way that occludes multiple neutralization targets located both within and outside of the V3 domain, and may reflect an alternative mechanism for neutralization resistance that is particularly active in subtype C and related isolates.