GADD34 attenuates HIV-1 replication by viral 5'-UTR TAR RNA-mediated translational inhibition.
5' Untranslated Regions
Gene Expression
Gene Knockdown Techniques
HIV Infections
/ metabolism
HIV Long Terminal Repeat
HIV-1
/ physiology
Host-Pathogen Interactions
Humans
Peptide Chain Initiation, Translational
Protein Phosphatase 1
/ genetics
RNA, Small Interfering
/ genetics
RNA, Viral
/ chemistry
Virus Replication
tat Gene Products, Human Immunodeficiency Virus
/ metabolism
GADD34
HIV-1
HIV-1 5′-UTR
HIV-1 TAR RNA
Translation
Journal
Virology
ISSN: 1096-0341
Titre abrégé: Virology
Pays: United States
ID NLM: 0110674
Informations de publication
Date de publication:
15 01 2020
15 01 2020
Historique:
received:
26
08
2019
revised:
07
11
2019
accepted:
08
11
2019
pubmed:
30
11
2019
medline:
8
9
2020
entrez:
29
11
2019
Statut:
ppublish
Résumé
Role of GADD34, a protein that is induced following cellular stress, in HIV-1 replication was investigated. GADD34 was induced during the late phase of HIV-1 infection. siRNA-knockdown of GADD34 stimulated whereas overexpression of GADD34 inhibited HIV-1 replication. GADD34 N-terminal ER-binding-helix amino acid region 1-192 alone was found to be sufficient for the inhibition of HIV-1 replication whereas protein-phosphatase -1-binding domain and eIF-2α-phosphatase activity of GADD34 were not crucial for anti-HIV-1 activity. GADD34 did not alter the HIV-1 RNA levels but reduced the viral protein expression suggesting that GADD34 interferes in HIV protein synthesis. Studies on the effect of HIV-1-5'-UTR and its mutants on a human promoter-driven luciferase expression indicated that GADD34-inhibition was mediated by 5'-UTR/TAR RNA, probably by modulating TAR RNA structure. In summary, our data support a novel function of GADD34 as a putative anti-HIV-1 restriction factor.
Identifiants
pubmed: 31778897
pii: S0042-6822(19)30318-6
doi: 10.1016/j.virol.2019.11.010
pmc: PMC6957764
mid: NIHMS1545364
pii:
doi:
Substances chimiques
5' Untranslated Regions
0
RNA, Small Interfering
0
RNA, Viral
0
tat Gene Products, Human Immunodeficiency Virus
0
PPP1R15A protein, human
EC 3.1.3.16
Protein Phosphatase 1
EC 3.1.3.16
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
119-131Subventions
Organisme : CCR NIH HHS
ID : HHSN261200800001C
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.