Bobo Wing-Yee Mok, Maxwell Kwok, Hung Sing Li, Lowell Ling, Angel Lai, Bin Yan, Cherie Tsz-Yiu Law, Chui Him Yeung, Anna Jinxia Zhang, Rachel Chun-Yee Tam, Anja Kukic, Conor J Cremin, Yajie Zhang, Teng Long, Zhisen Kang, Ruibang Luo, Kam Tong Leung, Albert M Li, Grace Lui, Stephen Kwok-Wing Tsui, Jasper Fuk-Woo Chan, Kelvin Kai-Wang To, Paul K S Chan, Bryan P Yan, Honglin Chen, Ellen Ngar-Yun Poon
{"title":"SARS-CoV-2 变体在体外和体内对心肌细胞造成不同程度的感染和损伤。","authors":"Bobo Wing-Yee Mok, Maxwell Kwok, Hung Sing Li, Lowell Ling, Angel Lai, Bin Yan, Cherie Tsz-Yiu Law, Chui Him Yeung, Anna Jinxia Zhang, Rachel Chun-Yee Tam, Anja Kukic, Conor J Cremin, Yajie Zhang, Teng Long, Zhisen Kang, Ruibang Luo, Kam Tong Leung, Albert M Li, Grace Lui, Stephen Kwok-Wing Tsui, Jasper Fuk-Woo Chan, Kelvin Kai-Wang To, Paul K S Chan, Bryan P Yan, Honglin Chen, Ellen Ngar-Yun Poon","doi":"10.1186/s13578-024-01280-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>COVID-19 can cause cardiac complications and the latter are associated with poor prognosis and increased mortality. SARS-CoV-2 variants differ in their infectivity and pathogenicity, but how they affect cardiomyocytes (CMs) is unclear.</p><p><strong>Methods: </strong>The effects of SARS-CoV-2 variants were investigated using human induced pluripotent stem cell-derived (hiPSC-) CMs in vitro and Golden Syrian hamsters in vivo.</p><p><strong>Results: </strong>Different variants exhibited distinct tropism, mechanism of viral entry and pathology in the heart. Omicron BA.2 most efficiently infected and injured CMs in vitro and in vivo, and induced expression changes consistent with increased cardiac dysfunction, compared to other variants tested. Bioinformatics and upstream regulator analyses identified transcription factors and network predicted to control the unique transcriptome of Omicron BA.2 infected CMs. Increased infectivity of Omicron BA.2 is attributed to its ability to infect via endocytosis, independently of TMPRSS2, which is absent in CMs.</p><p><strong>Conclusions: </strong>In this study, we reveal previously unknown differences in how different SARS-CoV-2 variants affect CMs. Omicron BA.2, which is generally thought to cause mild disease, can damage CMs in vitro and in vivo. Our study highlights the need for further investigations to define the pathogenesis of cardiac complications arising from different SARS-CoV-2 variants.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"14 1","pages":"101"},"PeriodicalIF":6.1000,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297708/pdf/","citationCount":"0","resultStr":"{\"title\":\"SARS-CoV-2 variants divergently infect and damage cardiomyocytes in vitro and in vivo.\",\"authors\":\"Bobo Wing-Yee Mok, Maxwell Kwok, Hung Sing Li, Lowell Ling, Angel Lai, Bin Yan, Cherie Tsz-Yiu Law, Chui Him Yeung, Anna Jinxia Zhang, Rachel Chun-Yee Tam, Anja Kukic, Conor J Cremin, Yajie Zhang, Teng Long, Zhisen Kang, Ruibang Luo, Kam Tong Leung, Albert M Li, Grace Lui, Stephen Kwok-Wing Tsui, Jasper Fuk-Woo Chan, Kelvin Kai-Wang To, Paul K S Chan, Bryan P Yan, Honglin Chen, Ellen Ngar-Yun Poon\",\"doi\":\"10.1186/s13578-024-01280-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>COVID-19 can cause cardiac complications and the latter are associated with poor prognosis and increased mortality. SARS-CoV-2 variants differ in their infectivity and pathogenicity, but how they affect cardiomyocytes (CMs) is unclear.</p><p><strong>Methods: </strong>The effects of SARS-CoV-2 variants were investigated using human induced pluripotent stem cell-derived (hiPSC-) CMs in vitro and Golden Syrian hamsters in vivo.</p><p><strong>Results: </strong>Different variants exhibited distinct tropism, mechanism of viral entry and pathology in the heart. Omicron BA.2 most efficiently infected and injured CMs in vitro and in vivo, and induced expression changes consistent with increased cardiac dysfunction, compared to other variants tested. Bioinformatics and upstream regulator analyses identified transcription factors and network predicted to control the unique transcriptome of Omicron BA.2 infected CMs. Increased infectivity of Omicron BA.2 is attributed to its ability to infect via endocytosis, independently of TMPRSS2, which is absent in CMs.</p><p><strong>Conclusions: </strong>In this study, we reveal previously unknown differences in how different SARS-CoV-2 variants affect CMs. Omicron BA.2, which is generally thought to cause mild disease, can damage CMs in vitro and in vivo. Our study highlights the need for further investigations to define the pathogenesis of cardiac complications arising from different SARS-CoV-2 variants.</p>\",\"PeriodicalId\":49095,\"journal\":{\"name\":\"Cell and Bioscience\",\"volume\":\"14 1\",\"pages\":\"101\"},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2024-08-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297708/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell and Bioscience\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s13578-024-01280-y\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell and Bioscience","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s13578-024-01280-y","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
SARS-CoV-2 variants divergently infect and damage cardiomyocytes in vitro and in vivo.
Background: COVID-19 can cause cardiac complications and the latter are associated with poor prognosis and increased mortality. SARS-CoV-2 variants differ in their infectivity and pathogenicity, but how they affect cardiomyocytes (CMs) is unclear.
Methods: The effects of SARS-CoV-2 variants were investigated using human induced pluripotent stem cell-derived (hiPSC-) CMs in vitro and Golden Syrian hamsters in vivo.
Results: Different variants exhibited distinct tropism, mechanism of viral entry and pathology in the heart. Omicron BA.2 most efficiently infected and injured CMs in vitro and in vivo, and induced expression changes consistent with increased cardiac dysfunction, compared to other variants tested. Bioinformatics and upstream regulator analyses identified transcription factors and network predicted to control the unique transcriptome of Omicron BA.2 infected CMs. Increased infectivity of Omicron BA.2 is attributed to its ability to infect via endocytosis, independently of TMPRSS2, which is absent in CMs.
Conclusions: In this study, we reveal previously unknown differences in how different SARS-CoV-2 variants affect CMs. Omicron BA.2, which is generally thought to cause mild disease, can damage CMs in vitro and in vivo. Our study highlights the need for further investigations to define the pathogenesis of cardiac complications arising from different SARS-CoV-2 variants.
期刊介绍：
Cell and Bioscience, the official journal of the Society of Chinese Bioscientists in America, is an open access, peer-reviewed journal that encompasses all areas of life science research.
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