PMID- 36026486
OWN - NLM
STAT- MEDLINE
DCOM- 20220913
LR  - 20220927
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 18
IP  - 8
DP  - 2022 Aug
TI  - Echovirus 11 infection induces pyroptotic cell death by facilitating NLRP3 
      inflammasome activation.
PG  - e1010787
LID - 10.1371/journal.ppat.1010787 [doi]
LID - e1010787
AB  - Echovirus 11 (ECHO 11) is a positive-strand RNA virus belonging to the genus 
      Enterovirus of the family Picornaviridae. ECHO 11 infections can cause severe 
      inflammatory illnesses in neonates, including severe acute hepatitis with 
      coagulopathy. The activation of NLRP3 inflammasome is important for host defense 
      against invading viruses, which also contributes to viral pathogenicity. However, 
      whether and how ECHO 11 induces NLRP3 inflammasome activation remains unclear. In 
      this study, we isolated a clinical strain of ECHO 11 from stools of an ECHO 
      11-infected newborn patient with necrotizing hepatitis. This virus shared 99.95% 
      sequence identity with the previously published ECHO 11 sequence. The clinically 
      isolated ECHO 11 can efficiently infect liver cells and strongly induces 
      inflammation. Moreover, we showed that ECHO 11 induced IL-1beta secretion and 
      pyroptosis in cells and mouse bone marrow-derived macrophages (BMDMs). 
      Furthermore, ECHO 11 infection triggered NLRP3 inflammasome activation, as 
      evidenced by cleavages of GSDMD, pro-IL-1beta and pro-caspase-1, and the release of 
      LDH. ECHO 11 2B protein was required for NLRP3 inflammasome activation via 
      interacting with NLRP3 to facilitate the inflammasome complex assembly. In vivo, 
      expression of ECHO 11 2B also activated NLRP3 inflammasome in the murine liver. 
      Besides, 2Bs of multiple EVs can also interact with NLRP3 and induce NLRP3 
      inflammasome activation. Together, our findings demonstrate a mechanism by which 
      ECHO 11 induces inflammatory responses by activating NLRP3 inflammasome, 
      providing novel insights into the pathogenesis of ECHO 11 infection.
FAU - Wang, Chong
AU  - Wang C
AD  - Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, 
      Guangzhou, Guangdong, China.
AD  - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of 
      Sciences, Wuhan, Hubei, China.
FAU - Yang, Ruyi
AU  - Yang R
AD  - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of 
      Sciences, Wuhan, Hubei, China.
FAU - Yang, Fengxia
AU  - Yang F
AD  - Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, 
      Guangzhou, Guangdong, China.
FAU - Han, Yang
AU  - Han Y
AD  - Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology & 
      Wuhan Jinyintan Hospital, Wuhan Jinyintan Hospital, Wuhan, Hubei, China.
FAU - Ren, Yujie
AU  - Ren Y
AD  - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of 
      Sciences, Wuhan, Hubei, China.
FAU - Xiong, Xiaobei
AU  - Xiong X
AD  - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of 
      Sciences, Wuhan, Hubei, China.
FAU - Wang, Xingyun
AU  - Wang X
AD  - Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, 
      Guangzhou, Guangdong, China.
FAU - Bi, Yidan
AU  - Bi Y
AD  - Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, 
      Guangzhou, Guangdong, China.
FAU - Li, Lijun
AU  - Li L
AD  - Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, 
      Guangzhou, Guangdong, China.
FAU - Qiu, Yang
AU  - Qiu Y
AD  - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of 
      Sciences, Wuhan, Hubei, China.
FAU - Xu, Yi
AU  - Xu Y
AD  - Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, 
      Guangzhou, Guangdong, China.
FAU - Zhou, Xi
AU  - Zhou X
AUID- ORCID: 0000-0002-3846-5079
AD  - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of 
      Sciences, Wuhan, Hubei, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220826
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
SB  - IM
MH  - Animals
MH  - Enterovirus B, Human
MH  - *Inflammasomes/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Macrophages/metabolism
MH  - Mice
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism
MH  - *Pyroptosis
PMC - PMC9455886
COIS- The authors have declared that no competing interests exist.
EDAT- 2022/08/27 06:00
MHDA- 2022/09/14 06:00
PMCR- 2022/08/26
CRDT- 2022/08/26 14:46
PHST- 2022/02/03 00:00 [received]
PHST- 2022/08/01 00:00 [accepted]
PHST- 2022/09/08 00:00 [revised]
PHST- 2022/08/27 06:00 [pubmed]
PHST- 2022/09/14 06:00 [medline]
PHST- 2022/08/26 14:46 [entrez]
PHST- 2022/08/26 00:00 [pmc-release]
AID - PPATHOGENS-D-22-00213 [pii]
AID - 10.1371/journal.ppat.1010787 [doi]
PST - epublish
SO  - PLoS Pathog. 2022 Aug 26;18(8):e1010787. doi: 10.1371/journal.ppat.1010787. 
      eCollection 2022 Aug.