Changes in the V1 Loop of HIV-1 Envelope Glycoproteins Can Allosterically Modulate the Trimer Association Domain and Reduce PGT145 Sensitivity

Héctor Cervera, Sneha Ratnapriya, Angela Chov, Alon Herschhorn

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Human immunodeficiency virus (HIV-1) envelope glycoproteins (Envs) are a main focus of immunogen design and vaccine development. Broadly neutralizing antibodies (bnAbs) against HIV-1 Envs target conserved epitopes and neutralize multiple HIV-1 viral strains. Nevertheless, application of bnAbs to therapy and prevention is limited by resistant strains that are developed or preexist within the viral population. Here we studied the HIV-1NAB9 Envs that were isolated from a person who injects drugs and exhibits high and broad resistance to multiple bnAbs. We identified an insertion of 11 amino acids in the V1 loop that allosterically modulates HIV-1NAB9 sensitivity to the PGT145 bnAb, which targets the Env trimer association domain and supports high level viral infectivity. Our data provide new insights into the mechanisms of HIV-1 resistance to bnAbs and into allosteric connectivity between different HIV-1 Env domains.

Original languageEnglish (US)
Pages (from-to)1558-1568
Number of pages11
JournalACS Infectious Diseases
Volume7
Issue number6
DOIs
StatePublished - Jun 11 2021

Bibliographical note

Funding Information:
We thank Peter Rusert and Alexandra Trkola from the Institute of Medical Virology, University of Zurich, for providing the HIV-1 Env-expression plasmid. We also thank the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH for providing the following anti-HIV-1 Env antibodies: PGT145, PG9, PGT128, and the psPAX2 plasmid. This work was supported by NIH/NIDA grant 1DP2DA049279-01 to A.H. Molecular graphics and analyses performed with UCSF Chimera, which is supported by NIH P41-GM103311. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NAB9

Publisher Copyright:
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Keywords

  • broadly neutralizing antibodies
  • entry inhibition
  • envelope glycoproteins
  • HIV-1

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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