PMID- 34452454
OWN - NLM
STAT- MEDLINE
DCOM- 20220127
LR  - 20220127
IS  - 1999-4915 (Electronic)
IS  - 1999-4915 (Linking)
VI  - 13
IP  - 8
DP  - 2021 Aug 11
TI  - Coxsackievirus A2 Leads to Heart Injury in a Neonatal Mouse Model.
LID - 10.3390/v13081588 [doi]
LID - 1588
AB  - Coxsackievirus A2 (CVA2) has emerged as an active pathogen that has been 
      implicated in hand, foot, and mouth disease (HFMD) and herpangina outbreaks 
      worldwide. It has been reported that severe cases with CVA2 infection develop 
      into heart injury, which may be one of the causes of death. However, the 
      mechanisms of CVA2-induced heart injury have not been well understood. In this 
      study, we used a neonatal mouse model of CVA2 to investigate the possible 
      mechanisms of heart injury. We detected CVA2 replication and apoptosis in heart 
      tissues from infected mice. The activity of total aspartate transaminase (AST) 
      and lactate dehydrogenase (LDH) was notably increased in heart tissues from 
      infected mice. CVA2 infection also led to the disruption of cell-matrix 
      interactions in heart tissues, including the increases of matrix 
      metalloproteinase (MMP)3, MMP8, MMP9, connective tissue growth factor (CTGF) and 
      tissue inhibitors of metalloproteinases (TIMP)4. Infiltrating leukocytes (CD45(+) 
      and CD11b(+) cells) were observed in heart tissues of infected mice. 
      Correspondingly, the expression levels of inflammatory cytokines in tissue 
      lysates of hearts, including tumor necrosis factor alpha (TNF-alpha), 
      interleukin-1beta (IL-1beta), IL6 and monocyte chemoattractant protein-1 (MCP-1) 
      were significantly elevated in CVA2 infected mice. Inflammatory signal pathways 
      in heart tissues, including phosphatidylinositol 3-kinase (PI3K)-AKT, 
      mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-kappaB), were 
      also activated after infection. In summary, CVA2 infection leads to heart injury 
      in a neonatal mouse model, which might be related to viral replication, increased 
      expression levels of MMP-related enzymes and excessive inflammatory responses.
FAU - Ji, Wangquan
AU  - Ji W
AD  - Department of Epidemiology, College of Public Health, Zhengzhou University, 
      Zhengzhou 450001, China.
FAU - Zhu, Peiyu
AU  - Zhu P
AUID- ORCID: 0000-0003-2447-0827
AD  - Department of Epidemiology, College of Public Health, Zhengzhou University, 
      Zhengzhou 450001, China.
FAU - Liang, Ruonan
AU  - Liang R
AD  - Department of Epidemiology, College of Public Health, Zhengzhou University, 
      Zhengzhou 450001, China.
FAU - Zhang, Liang
AU  - Zhang L
AD  - Department of Epidemiology, College of Public Health, Zhengzhou University, 
      Zhengzhou 450001, China.
FAU - Zhang, Yu
AU  - Zhang Y
AD  - Department of Epidemiology, College of Public Health, Zhengzhou University, 
      Zhengzhou 450001, China.
FAU - Wang, Yuexia
AU  - Wang Y
AD  - Department of Epidemiology, College of Public Health, Zhengzhou University, 
      Zhengzhou 450001, China.
FAU - Zhang, Weiguo
AU  - Zhang W
AD  - Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
FAU - Tao, Ling
AU  - Tao L
AD  - School of Public Health, Xinxiang Medical University, Xinxiang 453003, China.
FAU - Chen, Shuaiyin
AU  - Chen S
AUID- ORCID: 0000-0001-6129-0310
AD  - Department of Epidemiology, College of Public Health, Zhengzhou University, 
      Zhengzhou 450001, China.
FAU - Yang, Haiyan
AU  - Yang H
AD  - Department of Epidemiology, College of Public Health, Zhengzhou University, 
      Zhengzhou 450001, China.
FAU - Jin, Yuefei
AU  - Jin Y
AUID- ORCID: 0000-0002-1523-0808
AD  - Department of Epidemiology, College of Public Health, Zhengzhou University, 
      Zhengzhou 450001, China.
FAU - Duan, Guangcai
AU  - Duan G
AD  - Department of Epidemiology, College of Public Health, Zhengzhou University, 
      Zhengzhou 450001, China.
AD  - Henan Key Laboratory of Molecular Medicine, Zhengzhou University, Zhengzhou 
      450001, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210811
PL  - Switzerland
TA  - Viruses
JT  - Viruses
JID - 101509722
RN  - 0 (Cytokines)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Apoptosis
MH  - Coxsackievirus Infections/*complications
MH  - Cytokines/classification/genetics/immunology
MH  - Disease Models, Animal
MH  - Enterovirus/classification/*pathogenicity
MH  - Heart/*virology
MH  - Heart Injuries/*virology
MH  - Inflammation/immunology/*virology
MH  - Matrix Metalloproteinases/classification/genetics/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Signal Transduction
PMC - PMC8402683
OTO - NOTNLM
OT  - coxsackievirus A2
OT  - hand, foot and mouth disease
OT  - heart injury
OT  - matrix metalloproteinase
COIS- The authors declare no conflict of interest.
EDAT- 2021/08/29 06:00
MHDA- 2022/01/28 06:00
PMCR- 2021/08/11
CRDT- 2021/08/28 01:06
PHST- 2021/06/07 00:00 [received]
PHST- 2021/07/30 00:00 [revised]
PHST- 2021/08/02 00:00 [accepted]
PHST- 2021/08/28 01:06 [entrez]
PHST- 2021/08/29 06:00 [pubmed]
PHST- 2022/01/28 06:00 [medline]
PHST- 2021/08/11 00:00 [pmc-release]
AID - v13081588 [pii]
AID - viruses-13-01588 [pii]
AID - 10.3390/v13081588 [doi]
PST - epublish
SO  - Viruses. 2021 Aug 11;13(8):1588. doi: 10.3390/v13081588.