Influenza A virus modulates ACE2 expression and SARS-CoV-2 infectivity in human cardiomyocytes

被引：4

作者：

Wu, Qian ^{[1
]}

Kumar, Naresh ^{[1
]}

Lafuse, William P. ^{[1
]}

Ahumada, Omar Santiagonunez ^{[1
]}

Saljoughian, Noushin ^{[1
]}

Whetstone, Elizabeth ^{[1
]}

Zani, Ashley ^{[1
]}

Patton, Ashley K. ^{[2
]}

El Refaey, Mona ^{[3
]}

Webb, Amy ^{[4
]}

Pietrzak, Maciej ^{[4
]}

Yu, Lianbo ^{[4
]}

Mahesh, K. C. ^{[5
,6
]}

Peeples, Mark E. ^{[5
,6
]}

Ganesan, Latha P. ^{[7
]}

Yount, Jacob S. ^{[1
]}

Rajaram, Murugesan V. S. ^{[1
]}

机构：

[1] Nationwide Childrens Hosp, Abigail Wexner Res Inst, Dept Microbial Infect & Immun, Columbus, OH 43209 USA

[2] Nationwide Childrens Hosp, Abigail Wexner Res Inst, Dept Pathol, Columbus, OH 43209 USA

[3] Nationwide Childrens Hosp, Abigail Wexner Res Inst, Dept Surg, Columbus, OH 43209 USA

[4] Nationwide Childrens Hosp, Abigail Wexner Res Inst, Dept Biomed Informat, Columbus, OH 43209 USA

[5] Nationwide Childrens Hosp, Abigail Wexner Res Inst, Dept Pediat, Columbus, OH 43209 USA

[6] Nationwide Childrens Hosp, Abigail Wexner Res Inst, Ctr Vaccines & Immun, Columbus, OH 43209 USA

[7] Ohio State Univ, Dept Internal Med, Wexner Med Ctr, Coll Med, Columbus, OH 43210 USA

来源：

ISCIENCE | 2022年 / 25卷 / 12期

关键词：

ENZYME; 2; ACE2; NITRIC-OXIDE; RECEPTOR; INHIBITION; REPLICATION; CELLS;

D O I：

10.1016/j.isci.2022.105701

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Influenza A virus (IAV) and SARS-CoV-2 virus are both acute respiratory viruses currently circulating in the human population. This study aims to determine the impact of IAV infection on SARS-CoV-2 pathogenesis and cardiomyocyte function. Infection of human bronchial epithelial cells (HBEC), A549 cells, lung fibroblasts (HLF), monocyte derived macrophages (MDMs), cardiac fibroblasts (HCF) and hiPSC-derived cardiomyocytes with IAV enhanced the expression of ACE2, the SARS-CoV-2 receptor. Similarly, IAV infection increased levels of ACE2 in the lungs of mice and humans. Of interest, we detected heavily glycosylated form of ACE2 in hiPSC-CMs and poorly glycosylated ACE2 in other cell types. Also, prior IAV infection enhances SARS-CoV-2 spike protein binding and viral entry in all cell types. However, efficient SARS-CoV-2 replication was uniquely inhibited in cardi-omyocytes. Glycosylation of ACE2 correlated with enzymatic conversion of its substrate Ang II, induction of eNOS and nitric oxide production, may provide a potential mechanism for the restricted SARS-CoV-2 replication in cardiomyocytes.

引用

页数：28

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