Cross-neutralizing crf01_ae-infected plasma from Malaysia targets cd4-binding site of human immunodeficiency virus type-1 envelope glycoprotein

Ng, Qi Ron and Tee, Kok Keng and Binley, James M. and Tong, Tommy (2022) Cross-neutralizing crf01_ae-infected plasma from Malaysia targets cd4-binding site of human immunodeficiency virus type-1 envelope glycoprotein. Aids Research and Human Retroviruses, 38 (2). pp. 162-172. ISSN 0889-2229, DOI https://doi.org/10.1089/aid.2020.0299.

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Abstract

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.

Item Type: Article
Funders: Sunway University, Malaysia [INT-FST-DBS-2016-02]
Uncontrolled Keywords: HIV-1; CRF01_AE; Neutralizing antibody; CD4-binding site
Subjects: Q Science > QR Microbiology
Q Science > QR Microbiology > QR355 Virology
R Medicine > R Medicine (General)
Divisions: Faculty of Medicine > Medicine Department
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 26 Apr 2022 05:09
Last Modified: 26 Apr 2022 05:09
URI: http://eprints.um.edu.my/id/eprint/33817

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