PMID- 34110282
OWN - NLM
STAT- MEDLINE
DCOM- 20211129
LR  - 20211129
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 10
DP  - 2021 Jun 10
TI  - Ubiquitination and degradation of NF90 by Tim-3 inhibits antiviral innate 
      immunity.
LID - 10.7554/eLife.66501 [doi]
LID - e66501
AB  - Nuclear factor 90 (NF90) is a novel virus sensor that serves to initiate 
      antiviral innate immunity by triggering stress granule (SG) formation. However, 
      the regulation of the NF90-SG pathway remains largely unclear. We found that 
      Tim-3, an immune checkpoint inhibitor, promotes the ubiquitination and 
      degradation of NF90 and inhibits NF90-SG-mediated antiviral immunity. Vesicular 
      stomatitis virus (VSV) infection induces the up-regulation and activation of 
      Tim-3 in macrophages, which in turn recruit the E3 ubiquitin ligase TRIM47 to the 
      zinc finger domain of NF90 and initiate a proteasome-dependent degradation via 
      K48-linked ubiquitination at Lys297. Targeted inactivation of Tim-3 enhances the 
      NF90 downstream SG formation by selectively increasing the phosphorylation of 
      protein kinase R and eukaryotic translation initiation factor 2alpha, the expression 
      of SG markers G3BP1 and TIA-1, and protecting mice from VSV challenge. These 
      findings provide insights into the crosstalk between Tim-3 and other receptors in 
      antiviral innate immunity and its related clinical significance.
CI  - (c) 2021, Dou et al.
FAU - Dou, Shuaijie
AU  - Dou S
AD  - Beijing Institute of Basic Medical Sciences, Beijing, China.
AD  - Anhui Medical University, Hefei, China.
FAU - Li, Guoxian
AU  - Li G
AD  - Beijing Institute of Basic Medical Sciences, Beijing, China.
AD  - Institute of Immunology, Medical School of Henan University, Kaifeng, China.
FAU - Li, Ge
AU  - Li G
AD  - Beijing Institute of Basic Medical Sciences, Beijing, China.
FAU - Hou, Chunmei
AU  - Hou C
AD  - Beijing Institute of Basic Medical Sciences, Beijing, China.
FAU - Zheng, Yang
AU  - Zheng Y
AD  - Department of Oncology, First Hospital of Jilin University, Changchun, China.
FAU - Tang, Lili
AU  - Tang L
AD  - Beijing Institute of Basic Medical Sciences, Beijing, China.
FAU - Gao, Yang
AU  - Gao Y
AD  - Beijing Institute of Basic Medical Sciences, Beijing, China.
FAU - Mo, Rongliang
AU  - Mo R
AD  - Beijing Institute of Basic Medical Sciences, Beijing, China.
FAU - Li, Yuxiang
AU  - Li Y
AD  - Beijing Institute of Basic Medical Sciences, Beijing, China.
FAU - Wang, Renxi
AU  - Wang R
AD  - Beijing Institute of Basic Medical Sciences, Beijing, China.
AD  - Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of 
      Science and Technology, Collaborative Innovation Center for Brain Disorders, 
      Capital Medical University, Beijing, China.
FAU - Shen, Beifen
AU  - Shen B
AD  - Beijing Institute of Basic Medical Sciences, Beijing, China.
FAU - Zhang, Jun
AU  - Zhang J
AD  - Institute of Immunology, Medical School of Henan University, Kaifeng, China.
FAU - Han, Gencheng
AU  - Han G
AUID- ORCID: 0000-0003-1408-878X
AD  - Beijing Institute of Basic Medical Sciences, Beijing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210610
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 0 (Havcr2 protein, mouse)
RN  - 0 (Hepatitis A Virus Cellular Receptor 2)
RN  - 0 (Nuclear Factor 90 Proteins)
SB  - IM
MH  - Animals
MH  - Cytoplasmic Granules/immunology/metabolism
MH  - *Hepatitis A Virus Cellular Receptor 2/immunology/metabolism
MH  - Immunity, Innate/*immunology
MH  - Macrophages/immunology/metabolism
MH  - Mice
MH  - *Nuclear Factor 90 Proteins/immunology/metabolism
MH  - Rhabdoviridae Infections/immunology
MH  - Ubiquitination/*immunology
MH  - Vesiculovirus
MH  - Virus Diseases/*immunology
PMC - PMC8225388
OTO - NOTNLM
OT  - NF90
OT  - Tim-3
OT  - antiviral innate immunity
OT  - immunology
OT  - inflammation
OT  - mouse
OT  - ubiquitination
OT  - virus sensor
COIS- SD, GL, GL, CH, YZ, LT, YG, RM, YL, RW, BS, JZ, GH No competing interests 
      declared
EDAT- 2021/06/11 06:00
MHDA- 2021/11/30 06:00
PMCR- 2021/06/10
CRDT- 2021/06/10 12:17
PHST- 2021/01/13 00:00 [received]
PHST- 2021/06/08 00:00 [accepted]
PHST- 2021/06/11 06:00 [pubmed]
PHST- 2021/11/30 06:00 [medline]
PHST- 2021/06/10 12:17 [entrez]
PHST- 2021/06/10 00:00 [pmc-release]
AID - 66501 [pii]
AID - 10.7554/eLife.66501 [doi]
PST - epublish
SO  - Elife. 2021 Jun 10;10:e66501. doi: 10.7554/eLife.66501.