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N-Acetyl Cysteine Alleviates Coxsackievirus B-Induced Myocarditis by Suppressing caspase-1

Yao Wang, Shuoxuan Zhao, Yang Chen, Ying Wang, Tianying Wang, Xiaoman Wo, Yanyan Dong, Jian Zhang, Weizhen Xu, Cong Qu, Xiaofeng Feng, Xiaoyu Wu, Yan Wang, Zhaohua Zhong, Wanran Zhao
doi: https://doi.org/10.1101/732677
Yao Wang
1Department of Cell Biology, Harbin Medical University, 157 Baojian Road, Harbin 150081, China
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Shuoxuan Zhao
1Department of Cell Biology, Harbin Medical University, 157 Baojian Road, Harbin 150081, China
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Yang Chen
2Department of Microbiology, Harbin Medical University, 157 Baojian Road, Harbin 150081, China
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Ying Wang
2Department of Microbiology, Harbin Medical University, 157 Baojian Road, Harbin 150081, China
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Tianying Wang
2Department of Microbiology, Harbin Medical University, 157 Baojian Road, Harbin 150081, China
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Xiaoman Wo
1Department of Cell Biology, Harbin Medical University, 157 Baojian Road, Harbin 150081, China
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Yanyan Dong
1Department of Cell Biology, Harbin Medical University, 157 Baojian Road, Harbin 150081, China
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Jian Zhang
1Department of Cell Biology, Harbin Medical University, 157 Baojian Road, Harbin 150081, China
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Weizhen Xu
2Department of Microbiology, Harbin Medical University, 157 Baojian Road, Harbin 150081, China
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Cong Qu
1Department of Cell Biology, Harbin Medical University, 157 Baojian Road, Harbin 150081, China
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Xiaofeng Feng
1Department of Cell Biology, Harbin Medical University, 157 Baojian Road, Harbin 150081, China
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Xiaoyu Wu
3Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin 150001, China
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Yan Wang
2Department of Microbiology, Harbin Medical University, 157 Baojian Road, Harbin 150081, China
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Zhaohua Zhong
2Department of Microbiology, Harbin Medical University, 157 Baojian Road, Harbin 150081, China
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  • For correspondence: zhaowr@hrbmu.edu.cn zhongzh@hrbmu.edu.cn
Wanran Zhao
1Department of Cell Biology, Harbin Medical University, 157 Baojian Road, Harbin 150081, China
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  • For correspondence: zhaowr@hrbmu.edu.cn zhongzh@hrbmu.edu.cn
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Abstract

Viral myocarditis caused by Coxsackievirus B (CVB) infection is a severe inflammatory disease of the myocardium, which may develop to cardiomyopathy and heart failure. No effective medicine is available to treat CVB infection. Here we evaluated the anti-CVB effect of N-acetyl cysteine (NAC), a widely used antioxidant. NAC significantly alleviated myocarditis and improved the overall condition of CVB type 3 (CVB3)-infected mice. Importantly, NAC treatment suppressed viral replication in both myocardium and cell culture. We show that NAC inhibited CVB3 replication when it was applied at the early stage of CVB3 infection. NAC’s antiviral mechanism, while independent of its antioxidant property, relies on its inhibition on caspase-1 activation, since the knockdown of caspase-1 blocked CVB3 replication. Moreover, NAC promotes procaspase-1 degradation via ubiquitin proteasome system, which may further contribute to the inhibited activity of caspase-1. NAC also inhibits the activity of viral proteases. Taken together, this study shows that NAC exerts potent anti-CVB effect by inhibiting caspase-1 and viral proteases. This study suggests that NAC can be a safe therapeutic option for CVB-induced myocarditis.

Footnotes

  • E-mail addresses of the authors: yaoxiaoyou1{at}126.com (Yao Wang), zhaoshuoxuan1{at}sina.com (S. Z.), cy_hmu{at}126.com (Y. C.), 18846132007{at}163.com (Ying Wang), wangty0929{at}163.com (T. W.), wxm0211{at}163.com (X. W.), hanyunxuan_dyy1992{at}hotmail.com (Y. D.), zhji1234e5{at}163.com (J. Z.), 18604502000{at}163.com (W. X), 271042033{at}qq.com (X. F.), 2921357921{at}qq.com (C. Q.), xiaoyu_wu2006{at}163.com, wangyan{at}hrbmu.edu.cn (Yan Wang) zhonghzh{at}hrbmu.edu.cn (Z. Z.), zhaowr{at}hrbmu.edu.cn (W. Z.)

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Posted August 12, 2019.
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N-Acetyl Cysteine Alleviates Coxsackievirus B-Induced Myocarditis by Suppressing caspase-1
Yao Wang, Shuoxuan Zhao, Yang Chen, Ying Wang, Tianying Wang, Xiaoman Wo, Yanyan Dong, Jian Zhang, Weizhen Xu, Cong Qu, Xiaofeng Feng, Xiaoyu Wu, Yan Wang, Zhaohua Zhong, Wanran Zhao
bioRxiv 732677; doi: https://doi.org/10.1101/732677
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N-Acetyl Cysteine Alleviates Coxsackievirus B-Induced Myocarditis by Suppressing caspase-1
Yao Wang, Shuoxuan Zhao, Yang Chen, Ying Wang, Tianying Wang, Xiaoman Wo, Yanyan Dong, Jian Zhang, Weizhen Xu, Cong Qu, Xiaofeng Feng, Xiaoyu Wu, Yan Wang, Zhaohua Zhong, Wanran Zhao
bioRxiv 732677; doi: https://doi.org/10.1101/732677

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