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

ACS infectious diseases 2021 Jun 11

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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.

Citation

Héctor Cervera, Sneha Ratnapriya, Angela Chov, Alon Herschhorn. Changes in the V1 Loop of HIV-1 Envelope Glycoproteins Can Allosterically Modulate the Trimer Association Domain and Reduce PGT145 Sensitivity. ACS infectious diseases. 2021 Jun 11;7(6):1558-1568