Antibody Recognition of CD4-Induced Open HIV-1 Env Trimers.
Animals
Humans
Mice
Antibodies, Monoclonal
/ metabolism
Antibodies, Neutralizing
/ metabolism
CD4 Antigens
/ metabolism
Cryoelectron Microscopy
HIV Antibodies
/ metabolism
HIV Envelope Protein gp120
/ metabolism
HIV Infections
/ immunology
HIV-1
Simian Immunodeficiency Virus
env Gene Products, Human Immunodeficiency Virus
Protein Binding
Protein Conformation
CD4i antibody
CG10 antibody
HIV-1 Env
V2i MAb
monoclonal antibodies
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
21 12 2022
21 12 2022
Historique:
pubmed:
1
12
2022
medline:
24
12
2022
entrez:
30
11
2022
Statut:
ppublish
Résumé
Human immunodeficiency virus type 1 (HIV-1) envelope (Env), a heterotrimer of gp120-gp41 subunits, mediates fusion of the viral and host cell membranes after interactions with the host receptor CD4 and a coreceptor. CD4 binding induces rearrangements in Env trimer, resulting in a CD4-induced (CD4i) open Env conformation. Structural studies of antibodies isolated from infected donors have defined antibody-Env interactions, with one class of antibodies specifically recognizing the CD4i open Env conformation. In this study, we characterized a group of monoclonal antibodies isolated from HIV-1 infected donors (V2i MAbs) that displayed characteristics of CD4i antibodies. Binding experiments demonstrated that the V2i MAbs preferentially recognize CD4-bound open Env trimers. Structural characterizations of V2i MAb-Env-CD4 trimer complexes using single-particle cryo-electron microscopy showed recognition by V2i MAbs using different angles of approach to the gp120 V1V2 domain and the β2/β3 strands on a CD4i open conformation Env with no direct interactions of the MAbs with CD4. We also characterized CG10, a CD4i antibody that was raised in mice immunized with a gp120-CD4 complex, bound to an Env trimer plus CD4. CG10 exhibited characteristics similar to those of the V2i antibodies, i.e., recognition of the open Env conformation, but showed direct contacts to both CD4 and gp120. Structural comparisons of these and previously characterized CD4i antibody interactions with Env provide a suggested mechanism for how these antibodies are elicited during HIV-1 infection.
Identifiants
pubmed: 36448805
doi: 10.1128/jvi.01082-22
pmc: PMC9769388
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
CD4 Antigens
0
HIV Antibodies
0
HIV Envelope Protein gp120
0
env Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0108222Subventions
Organisme : NIGMS NIH HHS
ID : P41 GM103393
Pays : United States
Organisme : HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : R01AI145655 (S.Z.P.)
Organisme : NIAID NIH HHS
ID : U54 AI170856
Pays : United States
Organisme : HHS | NIH | National Institute of General Medical Sciences (NIGMS)
ID : P50 AI150464 (P.J.B.)
Organisme : HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : HIVRAD P01 AI100148 (P.J.B.)
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