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Implications of the 375W mutation for HIV-1 tropism and vaccine development

Authors
  • Verdejo-Torres, Odette
  • Vargas-Pavia, Tania
  • Fatima, Syeda
  • Clapham, Paul R.
  • Duenas-Decamp, Maria J.
Type
Published Article
Journal
Journal of Virology
Publisher
American Society for Microbiology
Publication Date
Jan 03, 2024
Volume
98
Issue
1
Identifiers
DOI: 10.1128/jvi.01522-23
Source
ASM Journals
Keywords
License
Yellow

Abstract

Substitutions exposing the CD4 binding site (CD4bs) on HIV-1 trimers but still occluding non-neutralizing, immunogenic epitopes are desirable to develop HIV-1 vaccines. If such substitutions induce similar structural changes in trimers across diverse clades, they could be exploited for the development of multi-clade envelope (Env) vaccines. We show that the 375W substitution increases CD4 affinity for envelopes of all clades, circulating recombinant forms, and complex Envs tested, independent of disease stage. Clade B and C Envs with an exposed CD4bs were described for macrophage-tropic strains from the central nervous system (CNS). Here, we show that intermediate (clades C and D) and macrophage-tropic (clade G) envelopes can be detected outside the CNS. Vaccines targeting the CD4bs will be particularly effective against such strains and CNS disease.

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