N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03

Journal of Acquired Immune Deficiency Syndromes : JAIDS
Wenbo WangYouchun Wang

Abstract

HIV-1 gp120/gp41 is heavily modified by n-linked carbohydrates that play important roles either in correct folding or in shielding vulnerable viral protein surfaces from antibody recognition. In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. To further understand the functional role of these PNGS, we generated double and multiple mutants from selected individual PNGS mutants. The effects were then evaluated by examining infectivity and sensitivity to antibody-mediated neutralization by neutralizing monoclonal antibodies (nMAbs) and serum antibodies from HIV-1 positive donors. Infectivity results showed that, among the 12 combined PNGS mutants, only 197M.1 (N197D/N301Q) lost infectivity completely, whereas all others (except for 197M.6) showed reduced viral infectivity. In terms of neutralization sensitivity to known nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing N197D significantly increased neutralization sensitivity to VRC01 and VRC03, suggesting N197 and N463 have a strong synergistic effect in regulating the neutralizing s...Continue Reading

References

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Citations

Dec 21, 2019·Emerging Microbes & Infections·Jianhui NieYouchun Wang
Aug 22, 2021·Proceedings of the National Academy of Sciences of the United States of America·Emanuele AndreanoRino Rappuoli

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