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 |
Externí odkaz: |