Cited by 141SARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research StudiesChemokine receptors and signaling

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Upregulation of the Chemokine (C-C Motif) Ligand 2 via a Severe Acute Respiratory Syndrome Coronavirus Spike-ACE2 Signaling Pathway

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Chen, I-Yin, Chang, Shin C., Wu, Hung-Yi, Yu, Ting-Chun, Wei, Wen-Chin, Lin, Shiming, Chien, Chung-Liang, Chang, Ming-Fu·2010·Journal of Virology

DOI 10.1128/jvi.02560-09PMC PMC2897593

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Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV) was identified to be the causative agent of SARS with atypical pneumonia. Angiotensin-converting enzyme 2 (ACE2) is the major receptor for SARS-CoV. It is not clear whether ACE2 conveys signals from the cell surface to the nucleus and regulates expression of cellular genes upon SARS-CoV infection. To understand the pathogenesis of SARS-CoV, human type II pneumocyte (A549) cells were incubated with the viral spike protein or with SARS-CoV virus-like particles containing the viral spike protein to examine cytokine modulation in lung cells. Results from oligonucleotide-based microarray, real-time PCR, and enzyme-linked immunosorbent assays indicated an upregulation of the fibrosis-associated chemokine (C-C motif) ligand 2 (CCL2) by the viral spike protein and the virus-like particles. The upregulation of CCL2 by SARS-CoV spike protein was mainly mediated by extracellular signal-regulated kinase 1 and 2 (ERK1/2) and AP-1 but not the IκBα-NF-κB signaling pathway. In addition, Ras and Raf upstream of the ERK1/2 signaling pathway were involved in the upregulation of CCL2. Furthermore, ACE2 receptor was activated by casein kinase II-mediated phosphorylation in cells pretreated with the virus-like particles containing spike protein. These results indicate that SARS-CoV spike protein triggers ACE2 signaling and activates fibrosis-associated CCL2 expression through the Ras-ERK-AP-1 pathway.

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Authors: Chen, I.-Y., Chang, S. C., Wu, H.-Y., Yu, T.-C., Wei, W.-C., Lin, S., Chien, C.-L., & Chang, M.-F.
Affiliations: Institute of Biochemistry and Molecular Biology
Institute of Microbiology
Center for Optoelectronic Biomedicine
National Taiwan University (TW)
Corresponding author: Chang, Shin C.
Chang, Ming-Fu
ORCID: Wu, Hung-Yi
Chien, Chung-Liang
Chang, Ming-Fu
Venue: Journal of Virology
Publisher: American Society for Microbiology
Published: 2010-08
Volume: 84
Issue: 15
Pages: 7703-7712
ISSN: 0022-538X (ISSN-L)
1098-5514
DOI: 10.1128/jvi.02560-09
PMC: PMC2897593
OpenAlex: W2096549714
Cited by: 141
References: 45
Citations by year: 2026: 2 · 2025: 5 · 2024: 6 · 2023: 12 · 2022: 22 · 2021: 30 · 2020: 42 · 2019: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 2 · 2013: 1 · 2012: 2
FWCI: 1.45
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Journal of Virology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Science Council
Academia Sinica
National Taiwan University
National Cancer Institute
Topics: Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Keywords: SARS-CoV, ACE2 receptor, spike protein, MCP-1, ERK signaling, AP-1, RAS/RAF pathway, casein kinase 2, pulmonary fibrosis, A549 cells, SARS pathogenesis
MeSH terms: Angiotensin-Converting Enzyme 2, Cell Line, Enzyme-Linked Immunosorbent Assay, Epithelial Cells, Humans, Peptidyl-Dipeptidase A, Membrane Glycoproteins, Viral Envelope Proteins, Signal Transduction, Up-Regulation, Chemokine CCL2, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Severe acute respiratory syndrome-related coronavirus, Spike Glycoprotein, Coronavirus

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Upregulation of the Chemokine (C-C Motif) Ligand 2 via a Severe Acute Respiratory Syndrome Coronavirus Spike-ACE2 Signaling Pathway

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