Ligand accessibility to the HIV-1 Env co-receptor binding site can occur prior to CD4 engagement and is independent of viral tier category.

Abstract:

:HIV-1 virus entry into target cells requires the envelope glycoprotein (Env) to first bind the primary receptor, CD4 and subsequently the co-receptor. Antibody access to the co-receptor binding site (CoRbs) in the pre-receptor-engaged state, prior to cell attachment, remains poorly understood. Here, we have demonstrated that for tier-1 Envs, the CoRbs is directly accessible to full-length CD4-induced (CD4i) antibodies even before primary receptor engagement, indicating that on these Envs the CoRbs site is either preformed or can conformationally sample post-CD4-bound state. Tier-2 and tier-3 Envs, which are resistant to full-length CD4i antibody, are neutralized by m36.4, a lower molecular mass of CD4i-directed domain antibody. In some tier-2 and tier-3 Envs, CoRbs is accessible to m36.4 even prior to cellular attachment in an Env-specific manner independent of their tier category. These data suggest differential structural arrangements of CoRbs and varied masking of ligand access to the CoRbs in different Env isolates.

journal_name

Virology

journal_title

Virology

authors

Boliar S,Patil S,Shukla BN,Ghobbeh A,Deshpande S,Chen W,Guenaga J,Dimitrov DS,Wyatt RT,Chakrabarti BK

doi

10.1016/j.virol.2018.04.002

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

99-105

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(18)30110-7

journal_volume

519

pub_type

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