Human immunodeficiency virus type-1 (HIV-1) antigenic variation poses a great challenge for vaccine immunogen design to elicit broadly neutralizing antibodies (bNAbs). Over the last 10-15 years, great progress has been made to understand the conserved sites of sensitivity on HIV envelope glycoprotein spikes targeted by bNAbs. Plasma neutralization mapping and monoclonal antibody isolation efforts have revealed five major conserved epitope clusters. Most of this work has focused on subtype B and C-infected Caucasian or African donors. It is not clear if the same epitopes and epitope rank order preferences are also true in donors infected with different HIV-1 subtypes and with different racial backgrounds. To investigate this point, in this study we report the first attempt to profile the bNAb specificities of CRF01_AE-infected Malaysian plasmas. We first measured neutralization titers of 21 plasmas against a subtype A, B, and AE pseudovirus panel. This revealed that 14% (3 of 21) plasmas had cross-clade breadth. Focusing on the cross-neutralizing plasma P9, we used AE and JR-FL mutant pseudoviruses, gp120 monomer interference, and native polyacrylamide gel electrophoresis to better understand the neutralization specificity. P9 demonstrates CD4-binding-site specificity with trimer dependence and D368 independence.
Matched MeSH terms: HIV Envelope Protein gp120/genetics
The HIV-1 genetic variation in 60 infected Malaysian intravenous drug users (IDU) was studied by comparison of the nucleotide sequences and their predicted amino acid sequences in the V3 loop of the external glycoprotein gp120. In this study, HIV-1 B, C and E subtypes were identified among Malaysian IDU, with HIV-1 B being the predominant subtype (91.7%). HIV-1 C and HIV-1 E were minority subtypes among Malaysian IDU. Analysis of the amino acid alignment of the C2-V3 region of the env gene suggests a genetic relationship between Thai and Malaysian B and E subtype strains. This study serves as a baseline for monitoring HIV-1 genetic diversity and spread in Malaysia.
Matched MeSH terms: HIV Envelope Protein gp120/genetics*