Conserved Role of an N-Linked Glycan on the Surface Antigen of Human Immunodeficiency Virus Type 1 Modulating Virus Sensitivity to Broadly Neutralizing Antibodies against the Receptor and Coreceptor Binding Sites

摘要: UNLABELLED HIV-1 establishes persistent infection in part due to its ability evade host immune responses. Occlusion by glycans contributes masking conserved sites that are targets for some broadly neutralizing antibodies (bNAbs). Previous work has shown removal of a highly potential N-linked glycan (PNLG) site at amino acid residue 197 (N7) on the surface antigen gp120 increases neutralization sensitivity mutant virus CD4 binding (CD4bs)-directed compared wild-type (WT) counterpart. However, it is not clear if role N7 among diverse isolates and other regions Env display similar functions. In this work, we examined PNLGs region Env, particularly panel strains representing different clades, tissue origins, coreceptor usages, sensitivities. We demonstrate absence CD4bs- V3 loop-directed antibodies, indicating plays these epitopes. effect directed against V2 loop epitope isolate dependent. These findings indicate an important modulating structure, stability, or accessibility bNAb epitopes CD4bs region, thus target design immunogens therapeutics. IMPORTANCE envelope protein have been postulated contribute viral escape from specific recognition well defined. show here single unique exposure stability receptor without affecting integrity mediating bind CD4. The observation antigenicity can be modulated indicates select modification offers strategy vaccine candidates.