RNA-binding protein isoforms ZAP-S and ZAP-L have distinct antiviral and immune resolution functions.
Alphavirus Infections
/ genetics
Feedback, Physiological
HEK293 Cells
Hep G2 Cells
Homeostasis
Humans
Immunity, Innate
Interferon Regulatory Factor-3
/ genetics
Interferons
/ genetics
Protein Binding
Protein Isoforms
/ genetics
RNA
/ genetics
RNA, Small Interfering
/ genetics
RNA-Binding Proteins
/ genetics
Repressor Proteins
/ genetics
Sindbis Virus
/ physiology
Virus Replication
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
19
12
2018
accepted:
26
09
2019
pubmed:
20
11
2019
medline:
28
2
2020
entrez:
20
11
2019
Statut:
ppublish
Résumé
The initial response to viral infection is anticipatory, with host antiviral restriction factors and pathogen sensors constantly surveying the cell to rapidly mount an antiviral response through the synthesis and downstream activity of interferons. After pathogen clearance, the host's ability to resolve this antiviral response and return to homeostasis is critical. Here, we found that isoforms of the RNA-binding protein ZAP functioned as both a direct antiviral restriction factor and an interferon-resolution factor. The short isoform of ZAP bound to and mediated the degradation of several host interferon messenger RNAs, and thus acted as a negative feedback regulator of the interferon response. In contrast, the long isoform of ZAP had antiviral functions and did not regulate interferon. The two isoforms contained identical RNA-targeting domains, but differences in their intracellular localization modulated specificity for host versus viral RNA, which resulted in disparate effects on viral replication during the innate immune response.
Identifiants
pubmed: 31740798
doi: 10.1038/s41590-019-0527-6
pii: 10.1038/s41590-019-0527-6
pmc: PMC7240801
mid: NIHMS1586922
doi:
Substances chimiques
IRF3 protein, human
0
Interferon Regulatory Factor-3
0
Protein Isoforms
0
RNA, Small Interfering
0
RNA-Binding Proteins
0
Repressor Proteins
0
YLPM1 protein, human
0
RNA
63231-63-0
Interferons
9008-11-1
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
1610-1620Subventions
Organisme : NIAID NIH HHS
ID : R01 AI108765
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM133633
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI118916
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI135437
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007240
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007270
Pays : United States
Organisme : NIAID NIH HHS
ID : K22 AI119017
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI106677
Pays : United States
Organisme : NIH HHS
ID : S10 OD021490
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM069429
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI127463
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI104002
Pays : United States
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