Coxsackievirus B3 Infection Induces cyr61 Activation via JNK To Mediate Cell Death

Kim, Sun-Mi; Park, Jung-Hyun; Chung, Sun-Ku; Kim, Joo-Young; Hwang, Ha-Young; Chung, Kwang-Chul; Jo, Inho; Park, Sang-Ick; Nam, Jae-Hwan

doi:10.1128/jvi.78.24.13479-13488.2004

Cited by 70Viral Infections and Immunology ResearchCell death mechanisms and regulationSignaling Pathways in Disease

Coxsackievirus B3 Infection Induces cyr61 Activation via JNK To Mediate Cell Death

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Kim, Sun-Mi, Park, Jung-Hyun, Chung, Sun-Ku, Kim, Joo-Young, Hwang, Ha-Young, Chung, Kwang-Chul, Jo, Inho, Park, Sang-Ick +1 more·2004·Journal of Virology

DOI 10.1128/jvi.78.24.13479-13488.2004PMC PMC533934

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Abstract

Coxsackievirus B3 (CVB3), an enterovirus in the Picornavirus family, is the most common human pathogen associated with myocarditis and idiopathic dilated cardiomyopathy. We found upregulation of the cysteine-rich protein gene ( cyr61 ) after CVB3 infection in HeLa cells with a cDNA microarray approach, which is confirmed by Northern blot analysis. It is also revealed that the extracellular amount of Cyr61 protein was increased after CVB3 infection in HeLa cells. cyr61 is an early-transcribed gene, and the Cyr61 protein is secreted into the extracellular matrix. Its function is related to cell adhesion, migration, and neuronal cell death. Here, we show that activation of the cyr61 promoter by CVB3 infection is dependent on JNK activation induced by CVB3 replication and viral protein expression in infected cells. To explore the role of Cyr61 protein in infected HeLa cells, we transiently overexpressed cyr61 and infected HeLa cells with CVB3. This increased CVB3 growth in the cells and promoted host cell death by viral infection, whereas down-expression of cyr61 with short interfering RNA reduced CVB3 growth and showed resistance to cell death by CVB3 infection. In conclusion, we have demonstrated a new role for cyr61 in HeLa cells infected with CVB3, which is associated with the cell death induced by virus infection. These data thus expand our understanding of the physiological functions of cyr61 in virus-induced cell death and provide new insights into the cellular factors involved.

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CCN1 is induced by bacterial and viral infections and by inflammatory cytokines such as IL-1 and TNF-α.
“CCN1 is also induced by bacterial and viral infections [29–32], and by inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α) [33].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [29]
CCN1 expression is induced by bacterial and viral infections.
“CCN1 expression is induced by inflammatory cytokines such as IL-1 and TNF-α [33,131], as well as by bacterial and viral infections [29–32].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [29]

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Authors: Kim, S.-M., Park, J.-H., Chung, S.-K., Kim, J.-Y., Hwang, H.-Y., Chung, K.-C., Jo, I., Park, S.-I., & Nam, J.-H.
Affiliations: National Institutes of Health (US)
Yonsei University (KR)
ORCID: Park, Jung-Hyun
Chung, Sun-Ku
Kim, Joo-Young
Jo, Inho
Nam, Jae-Hwan
Venue: Journal of Virology
Publisher: American Society for Microbiology
Published: 2004-12-15
Volume: 78
Issue: 24
Pages: 13479-13488
ISSN: 0022-538X (ISSN-L)
1098-5514
DOI: 10.1128/jvi.78.24.13479-13488.2004
PMC: PMC533934
OpenAlex: W2005003131
Cited by: 70
References: 49
Citations by year: 2024: 2 · 2023: 3 · 2022: 3 · 2021: 1 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 4 · 2014: 6 · 2013: 2 · 2012: 2
FWCI: 3.05
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Journal of Virology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords: coxsackievirus B3, CYR61, JNK signaling, virus-induced cell death, HeLa cells, promoter activation, extracellular matrix, myocarditis, dilated cardiomyopathy, viral replication, host-virus interaction
MeSH terms: Gene Expression Regulation, HeLa Cells, Humans, Apoptosis, Immediate-Early Proteins, Enterovirus B, Human, Intercellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, Cysteine-Rich Protein 61

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Coxsackievirus B3 Infection Induces cyr61 Activation via JNK To Mediate Cell Death

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