Tumor necrosis factor-alpha exacerbates viral entry in SARS-CoV2-infected iPSC-derived cardiomyocytes

Chiu Yang Lee, Chih Heng Huang, Elham Rastegari, Vimalan Rengganaten, Ping Cheng Liu, Ping Hsing Tsai, Yuan Fan Chin, Jing Rong Wu, Shih Hwa Chiou, Yuan Chi Teng, Chih Wei Lee, Yanwen Liang, An Yu Chen, Shu Chen Hsu, Yi Jen Hung*, Jun Ren Sun, Chian Shiu Chien, Yueh Chien


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6 引文 斯高帕斯(Scopus)


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.

期刊International Journal Of Molecular Sciences
出版狀態Published - 9月 2021


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