The V2 domain of HIV gp120 mimics an interaction between CD4 and integrin ⍺4β7.

Autor: Van Ryk D; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America., Vimonpatranon S; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America.; Department of Retrovirology, Armed Forces Research Institute of Medical Sciences-United States Component, Bangkok, Thailand., Hiatt J; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America., Ganesan S; Biological Imaging Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America., Chen N; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America., McMurry J; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America., Garba S; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America., Min S; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America., Goes LR; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America.; Oncovirology Program, Instituto Nacional de Câncer, Rio de Janeiro, Rio de Janeiro, Brazil., Girard A; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America., Yolitz J; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America., Licavoli I; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America., Wei D; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America., Huang D; Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, Maryland, United States of America., Soares MA; Oncovirology Program, Instituto Nacional de Câncer, Rio de Janeiro, Rio de Janeiro, Brazil.; Department of Genetics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Martinelli E; Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America., Cicala C; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America., Arthos J; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2023 Dec 08; Vol. 19 (12), pp. e1011860. Date of Electronic Publication: 2023 Dec 08 (Print Publication: 2023).
DOI: 10.1371/journal.ppat.1011860
Abstrakt: The CD4 receptor, by stabilizing TCR-MHC II interactions, plays a central role in adaptive immunity. It also serves as the HIV docking receptor. The HIV gp120 envelope protein binds directly to CD4. This interaction is a prerequisite for viral entry. gp120 also binds to ⍺4β7, an integrin that is expressed on a subset of memory CD4+ T cells. HIV tropisms for CD4+ T cells and gut tissues are central features of HIV pathogenesis. We report that CD4 binds directly to ⍺4β7 in a dynamic way, consistent with a cis regulatory interaction. The molecular details of this interaction are related to the way in which gp120 interacts with both receptors. Like MAdCAM-1 and VCAM-1, two recognized ligands of ⍺4β7, the binding interface on CD4 includes 2 sites (1° and accessory), distributed across its two N-terminal IgSF domains (D1 and D2). The 1° site includes a sequence in the G β-strand of CD4 D2, KIDIV, that binds directly to ⍺4β7. This pentapeptide sequence occurs infrequently in eukaryotic proteins. However, a closely related and conserved sequence, KLDIV, appears in the V2 domain of gp120. KLDIV mediates gp120-⍺4β7 binding. The accessory ⍺4β7 binding site on CD4 includes Phe43. The Phe43 aromatic ring protrudes outward from one edge of a loop connecting the C'C" strands of CD4 D1. Phe43 is a principal contact for HIV gp120. It interacts with conserved residues in the recessed CD4 binding pocket. Substitution of Phe43 abrogates CD4 binding to both gp120 and ⍺4β7. As such, the interactions of gp120 with both CD4 and ⍺4β7 reflect elements of their interactions with each other. These findings indicate that gp120 specificities for CD4 and ⍺4β7 are interrelated and suggest that selective pressures which produced a CD4 tropic virus that replicates in gut tissues are linked to a dynamic interaction between these two receptors.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)
Databáze: MEDLINE
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