Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity.
Alleles
CD4 Antigens
/ metabolism
Cell Line, Tumor
Down-Regulation
Gene Knockout Techniques
HIV Infections
/ genetics
HIV-1
/ genetics
HLA-A Antigens
/ metabolism
Host-Pathogen Interactions
/ genetics
Humans
Membrane Proteins
/ antagonists & inhibitors
Mutation
Polymorphism, Genetic
T-Lymphocytes
/ metabolism
Virion
/ metabolism
Virulence
/ genetics
Virus Internalization
Virus Replication
/ genetics
nef Gene Products, Human Immunodeficiency Virus
/ genetics
HIV-1 Nef
elite controllers
host restriction
serine incorporator
viral infectivity
viral pathogenesis
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
05 11 2019
05 11 2019
Historique:
received:
01
05
2018
revised:
26
07
2019
accepted:
01
10
2019
entrez:
7
11
2019
pubmed:
7
11
2019
medline:
25
9
2020
Statut:
ppublish
Résumé
HIV-1 Nef enhances virion infectivity by counteracting host restriction factor SERINC5; however, the impact of natural Nef polymorphisms on this function is largely unknown. We characterize SERINC5 downregulation activity of 91 primary HIV-1 subtype B nef alleles, including isolates from 45 elite controllers and 46 chronic progressors. Controller-derived Nef clones display lower ability to downregulate SERINC5 (median 80% activity) compared with progressor-derived clones (median 96% activity) (p = 0.0005). We identify 18 Nef polymorphisms associated with differential function, including two CTL escape mutations that contribute to lower SERINC5 downregulation: K94E, driven by HLA-B
Identifiants
pubmed: 31693887
pii: S2211-1247(19)31300-2
doi: 10.1016/j.celrep.2019.10.007
pmc: PMC6925589
mid: NIHMS1542670
pii:
doi:
Substances chimiques
CD4 Antigens
0
HLA-A Antigens
0
Membrane Proteins
0
SERINC5 protein, human
0
nef Gene Products, Human Immunodeficiency Virus
0
nef protein, Human immunodeficiency virus 1
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1449-1457.e5Subventions
Organisme : NIAID NIH HHS
ID : R01 AI127263
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI126617
Pays : United States
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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