CD4 receptor diversity represents an ancient protection mechanism against primate lentiviruses.
Acquired Immunodeficiency Syndrome
/ genetics
Alleles
Animals
CD4 Antigens
/ chemistry
Catarrhini
/ genetics
Evolution, Molecular
Gene Products, env
/ chemistry
Genetic Variation
HIV
Humans
Protein Binding
Protein Domains
Simian Acquired Immunodeficiency Syndrome
/ genetics
Simian Immunodeficiency Virus
CD4
balancing selection
parallel evolution
primate lentiviruses
trans-specific polymorphism
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
30 03 2021
30 03 2021
Historique:
entrez:
27
3
2021
pubmed:
28
3
2021
medline:
27
10
2021
Statut:
ppublish
Résumé
Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. Here, we show that within-species CD4 diversity is not unique to chimpanzees but found in many African primate species. Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. D1 domain amino acid replacements affected SIV Env-mediated cell entry in a single-round infection assay, restricting infection in a strain- and allele-specific fashion. Several identical CD4 polymorphisms, including the addition of
Identifiants
pubmed: 33771926
pii: 2025914118
doi: 10.1073/pnas.2025914118
pmc: PMC8020793
pii:
doi:
Substances chimiques
CD4 Antigens
0
Gene Products, env
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : T32 AI007632
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG023122
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG024824
Pays : United States
Organisme : NIH HHS
ID : P51 OD011104
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI045008
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI120810
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI131251
Pays : United States
Organisme : NCRR NIH HHS
ID : P51 RR000164
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI150590
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI131331
Pays : United States
Organisme : NIAID NIH HHS
ID : R33 AI133696
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI160607
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI165080
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI050529
Pays : United States
Informations de copyright
Copyright © 2021 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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