Tumor Necrosis Factor-Alpha Exacerbates Viral Entry in SARS-CoV2-Infected iPSC-Derived Cardiomyocytes

Autor: Shih Hwa Chiou, Chiu Yang Lee, An Yu Chen, Shu Chen Hsu, Chian Shiu Chien, Jing Rong Wu, Yuan Fan Chin, Yi Jen Hung, Yanwen Liang, Chih Wei Lee, Yuan Chi Teng, Jun Ren Sun, Ping Hsing Tsai, Yueh Chien, Vimalan Rengganaten, Chih Heng Huang, Elham Rastegari, Ping Cheng Liu
Jazyk: angličtina
Rok vydání: 2021
Předmět:
cardiomyocytes
Myocytes
Cardiac
Biology (General)
skin and connective tissue diseases
Spectroscopy
Serine Endopeptidases
Cell Differentiation
General Medicine
Computer Science Applications
Up-Regulation
Cytokine release syndrome
SARS-CoV2 pseudovirus
Chemistry
Cardiovascular Diseases
induce pluripotent stem cells
Tumor necrosis factor alpha
Angiotensin-Converting Enzyme 2
medicine.symptom
Cytokine Release Syndrome
QH301-705.5
Induced Pluripotent Stem Cells
Inflammation
Biology
Catalysis
Article
Proinflammatory cytokine
Cell Line
Inorganic Chemistry
Viral entry
medicine
Coronavirus Nucleocapsid Proteins
Humans
Physical and Theoretical Chemistry
Molecular Biology
QD1-999
SARS-CoV-2
Tumor Necrosis Factor-alpha
Myocardium
Organic Chemistry
fungi
Viral nucleocapsid
COVID-19
Computational Biology
Virus Internalization
medicine.disease
Phosphoproteins
Virology
body regions
Cell culture
inflammation
TNF-α
SARS-CoV2
Cytokine storm
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 9869, p 9869 (2021)
International Journal of Molecular Sciences
Volume 22
Issue 18
ISSN: 1661-6596
1422-0067
Popis: The coronavirus disease 2019 (COVID-19) pandemic with high infectivity and mortality has caused severe social and economic impacts worldwide. Growing reports of COVID-19 patients with multi-organ damage indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) may also disturb the cardiovascular system. Herein, we used human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) as the in vitro platform to examine the consequence of SARS-CoV2 infection on iCMs. Differentiated iCMs expressed the primary SARS-CoV2 receptor angiotensin-converting enzyme-II (ACE2) and the transmembrane protease serine type 2 (TMPRSS2) receptor suggesting the susceptibility of iCMs to SARS-CoV2. Following the infection of iCMs with SARS-CoV2, the viral nucleocapsid (N) protein was detected in the host cells, demonstrating the successful infection. Bioinformatics analysis revealed that the SARS-CoV2 infection upregulates several inflammation-related genes, including the proinflammatory cytokine tumor necrosis factor-α (TNF-α). The pretreatment of iCMs with TNF-α for 24 h, significantly increased the expression of ACE2 and TMPRSS2, SASR-CoV2 entry receptors. The TNF-α pretreatment enhanced the entry of GFP-expressing SARS-CoV2 pseudovirus into iCMs, and the neutralization of TNF-α ameliorated the TNF-α-enhanced viral entry. Collectively, SARS-CoV2 elevated TNF-α expression, which in turn enhanced the SARS-CoV2 viral entry. Our findings suggest that, TNF-α may participate in the cytokine storm and aggravate the myocardial damage in COVID-19 patients.
Databáze: OpenAIRE
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