Recombinant Human Thymosin Beta-4 Protects against Mouse Coronavirus Infection

Coronaviruses (CoVs) are enveloped and harbor an unusually large (30–32 kb) positive-strand linear RNA genome. Highly pathogenic coronaviruses cause severe acute respiratory syndrome (SARS) (SARS-CoV and SARS-CoV-2) and Middle East respiratory syndrome (MERS) (MERS-CoV) in humans. The coronavirus mo...

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Main Authors: Rui Yu, Yunyun Mao, Kai Li, Yanfang Zhai, Yue Zhang, Shuling Liu, Yuemei Gao, Zhengshan Chen, Yanhong Liu, Ting Fang, Mengsu Zhao, Ruihua Li, Junjie Xu, Wei Chen
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2021/9979032
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author Rui Yu
Yunyun Mao
Kai Li
Yanfang Zhai
Yue Zhang
Shuling Liu
Yuemei Gao
Zhengshan Chen
Yanhong Liu
Ting Fang
Mengsu Zhao
Ruihua Li
Junjie Xu
Wei Chen
author_facet Rui Yu
Yunyun Mao
Kai Li
Yanfang Zhai
Yue Zhang
Shuling Liu
Yuemei Gao
Zhengshan Chen
Yanhong Liu
Ting Fang
Mengsu Zhao
Ruihua Li
Junjie Xu
Wei Chen
author_sort Rui Yu
collection DOAJ
description Coronaviruses (CoVs) are enveloped and harbor an unusually large (30–32 kb) positive-strand linear RNA genome. Highly pathogenic coronaviruses cause severe acute respiratory syndrome (SARS) (SARS-CoV and SARS-CoV-2) and Middle East respiratory syndrome (MERS) (MERS-CoV) in humans. The coronavirus mouse hepatitis virus (MHV) infects mice and serves as an ideal model of viral pathogenesis, mainly because experiments can be conducted using animal-biosafety level-2 (A-BSL2) containment. Human thymosin beta-4 (Tβ4), a 43-residue peptide with an acetylated N-terminus, is widely expressed in human tissues. Tβ4 regulates actin polymerization and functions as an anti-inflammatory molecule and an antioxidant as well as a promoter of wound healing and angiogenesis. These activities led us to test whether Tβ4 serves to treat coronavirus infections of humans. To test this possibility, here, we established a BALB/c mouse model of coronavirus infection using mouse CoV MHV-A59 to evaluate the potential protective effect of recombinant human Tβ4 (rhTβ4). Such a system can be employed under A-BSL2 containment instead of A-BSL3 that is required to study coronaviruses infectious for humans. We found that rhTβ4 significantly increased the survival rate of mice infected with MHV-A59 through inhibiting virus replication, balancing the host’s immune response, alleviating pathological damage, and promoting repair of the liver. These results will serve as the basis for further application of rhTβ4 to the treatment of human CoV diseases such as COVID-19.
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publishDate 2021-01-01
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series Mediators of Inflammation
spelling doaj-art-8d1e6aa9a6ce4b11bd50d7de0a0a7a432025-08-20T02:09:34ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/99790329979032Recombinant Human Thymosin Beta-4 Protects against Mouse Coronavirus InfectionRui Yu0Yunyun Mao1Kai Li2Yanfang Zhai3Yue Zhang4Shuling Liu5Yuemei Gao6Zhengshan Chen7Yanhong Liu8Ting Fang9Mengsu Zhao10Ruihua Li11Junjie Xu12Wei Chen13Beijing Institute of Biotechnology, Beijing 100071, ChinaBeijing Institute of Biotechnology, Beijing 100071, ChinaBeijing Institute of Biotechnology, Beijing 100071, ChinaBeijing Institute of Biotechnology, Beijing 100071, ChinaBeijing Institute of Biotechnology, Beijing 100071, ChinaBeijing Institute of Biotechnology, Beijing 100071, ChinaBeijing Institute of Biotechnology, Beijing 100071, ChinaBeijing Institute of Biotechnology, Beijing 100071, ChinaBeijing Institute of Biotechnology, Beijing 100071, ChinaBeijing Institute of Biotechnology, Beijing 100071, ChinaBeijing Institute of Biotechnology, Beijing 100071, ChinaBeijing Institute of Biotechnology, Beijing 100071, ChinaBeijing Institute of Biotechnology, Beijing 100071, ChinaBeijing Institute of Biotechnology, Beijing 100071, ChinaCoronaviruses (CoVs) are enveloped and harbor an unusually large (30–32 kb) positive-strand linear RNA genome. Highly pathogenic coronaviruses cause severe acute respiratory syndrome (SARS) (SARS-CoV and SARS-CoV-2) and Middle East respiratory syndrome (MERS) (MERS-CoV) in humans. The coronavirus mouse hepatitis virus (MHV) infects mice and serves as an ideal model of viral pathogenesis, mainly because experiments can be conducted using animal-biosafety level-2 (A-BSL2) containment. Human thymosin beta-4 (Tβ4), a 43-residue peptide with an acetylated N-terminus, is widely expressed in human tissues. Tβ4 regulates actin polymerization and functions as an anti-inflammatory molecule and an antioxidant as well as a promoter of wound healing and angiogenesis. These activities led us to test whether Tβ4 serves to treat coronavirus infections of humans. To test this possibility, here, we established a BALB/c mouse model of coronavirus infection using mouse CoV MHV-A59 to evaluate the potential protective effect of recombinant human Tβ4 (rhTβ4). Such a system can be employed under A-BSL2 containment instead of A-BSL3 that is required to study coronaviruses infectious for humans. We found that rhTβ4 significantly increased the survival rate of mice infected with MHV-A59 through inhibiting virus replication, balancing the host’s immune response, alleviating pathological damage, and promoting repair of the liver. These results will serve as the basis for further application of rhTβ4 to the treatment of human CoV diseases such as COVID-19.http://dx.doi.org/10.1155/2021/9979032
spellingShingle Rui Yu
Yunyun Mao
Kai Li
Yanfang Zhai
Yue Zhang
Shuling Liu
Yuemei Gao
Zhengshan Chen
Yanhong Liu
Ting Fang
Mengsu Zhao
Ruihua Li
Junjie Xu
Wei Chen
Recombinant Human Thymosin Beta-4 Protects against Mouse Coronavirus Infection
Mediators of Inflammation
title Recombinant Human Thymosin Beta-4 Protects against Mouse Coronavirus Infection
title_full Recombinant Human Thymosin Beta-4 Protects against Mouse Coronavirus Infection
title_fullStr Recombinant Human Thymosin Beta-4 Protects against Mouse Coronavirus Infection
title_full_unstemmed Recombinant Human Thymosin Beta-4 Protects against Mouse Coronavirus Infection
title_short Recombinant Human Thymosin Beta-4 Protects against Mouse Coronavirus Infection
title_sort recombinant human thymosin beta 4 protects against mouse coronavirus infection
url http://dx.doi.org/10.1155/2021/9979032
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