Attenuation of mouse hepatitis virus by deletion of the LLRKxGxKG region of Nsp1.

Coronaviruses are a family of large positive-sense RNA viruses that are responsible for a wide range of important veterinary and human diseases. Nsp1 has been shown to have an important role in the pathogenetic mechanisms of coronaviruses in vivo. To assess the function of a relatively conserved dom...

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Main Authors: Lin Lei, Sun Ying, Luo Baojun, Yang Yi, He Xiang, Su Wenli, Sun Zounan, Guo Deyin, Zhu Qingyu, Liu Jingmei, Chang Guohui
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23593419/pdf/?tool=EBI
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author Lin Lei
Sun Ying
Luo Baojun
Yang Yi
He Xiang
Su Wenli
Sun Zounan
Guo Deyin
Zhu Qingyu
Liu Jingmei
Chang Guohui
author_facet Lin Lei
Sun Ying
Luo Baojun
Yang Yi
He Xiang
Su Wenli
Sun Zounan
Guo Deyin
Zhu Qingyu
Liu Jingmei
Chang Guohui
author_sort Lin Lei
collection DOAJ
description Coronaviruses are a family of large positive-sense RNA viruses that are responsible for a wide range of important veterinary and human diseases. Nsp1 has been shown to have an important role in the pathogenetic mechanisms of coronaviruses in vivo. To assess the function of a relatively conserved domain (LLRKxGxKG) of MHV nsp1, a mutant virus, MHV-nsp1-27D, with a 27 nts (LLRKxGxKG) deletion in nsp1, was constructed using a reverse genetic system with a vaccinia virus vector. The mutant virus had similar growth kinetics to MHV-A59 wild-type virus in 17CI-1 cells, but was highly attenuated in vivo. Moreover, the mutant virus completely protected C57BL/6 mice from a lethal MHV-A59 challenge. To further analyze the mechanism of the attenuation of the mutant virus, changes in reporter gene expression were measured in nsp1- or nsp1-27D-expressing cells; the results showed that nsp1 inhibited reporter gene expression controlled by different promoters, but that this inhibition was reduced for nsp1-27D. The research in vivo and in vitro suggests that the LLRKxGxKG region of nsp1 may play an important role in this process.
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spelling doaj.art-568bccf523a4441ba46f88fde068a5382022-12-21T23:09:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0184e6116610.1371/journal.pone.0061166Attenuation of mouse hepatitis virus by deletion of the LLRKxGxKG region of Nsp1.Lin LeiSun YingLuo BaojunYang YiHe XiangSu WenliSun ZounanGuo DeyinZhu QingyuLiu JingmeiChang GuohuiCoronaviruses are a family of large positive-sense RNA viruses that are responsible for a wide range of important veterinary and human diseases. Nsp1 has been shown to have an important role in the pathogenetic mechanisms of coronaviruses in vivo. To assess the function of a relatively conserved domain (LLRKxGxKG) of MHV nsp1, a mutant virus, MHV-nsp1-27D, with a 27 nts (LLRKxGxKG) deletion in nsp1, was constructed using a reverse genetic system with a vaccinia virus vector. The mutant virus had similar growth kinetics to MHV-A59 wild-type virus in 17CI-1 cells, but was highly attenuated in vivo. Moreover, the mutant virus completely protected C57BL/6 mice from a lethal MHV-A59 challenge. To further analyze the mechanism of the attenuation of the mutant virus, changes in reporter gene expression were measured in nsp1- or nsp1-27D-expressing cells; the results showed that nsp1 inhibited reporter gene expression controlled by different promoters, but that this inhibition was reduced for nsp1-27D. The research in vivo and in vitro suggests that the LLRKxGxKG region of nsp1 may play an important role in this process.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23593419/pdf/?tool=EBI
spellingShingle Lin Lei
Sun Ying
Luo Baojun
Yang Yi
He Xiang
Su Wenli
Sun Zounan
Guo Deyin
Zhu Qingyu
Liu Jingmei
Chang Guohui
Attenuation of mouse hepatitis virus by deletion of the LLRKxGxKG region of Nsp1.
PLoS ONE
title Attenuation of mouse hepatitis virus by deletion of the LLRKxGxKG region of Nsp1.
title_full Attenuation of mouse hepatitis virus by deletion of the LLRKxGxKG region of Nsp1.
title_fullStr Attenuation of mouse hepatitis virus by deletion of the LLRKxGxKG region of Nsp1.
title_full_unstemmed Attenuation of mouse hepatitis virus by deletion of the LLRKxGxKG region of Nsp1.
title_short Attenuation of mouse hepatitis virus by deletion of the LLRKxGxKG region of Nsp1.
title_sort attenuation of mouse hepatitis virus by deletion of the llrkxgxkg region of nsp1
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23593419/pdf/?tool=EBI
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