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Human norovirus ns3 has rna helicase and chaperoning activities
Li, Teng-Feng1,2; Hosmillo, Myra3; Schwanke, Hella3; Shu, Ting1,2; Wang, Zhaowei1,2; Yin, Lei2; Curry, Stephen4; Goodfellow, Ian G.3; Zhou, Xi1,2
刊名Journal of virology
2018-03-01
卷号92期号:5页码:18
关键词Rna chaperone Rna helicase Norovirus
ISSN号0022-538X
DOI10.1128/jvi.01606-17
通讯作者Zhou, xi(zhouxi@wh.iov.cn)
英文摘要Rna-remodeling proteins, including rna helicases and chaperones, act to remodel rna structures and/or protein-rna interactions and are required for all processes involving rnas. although many viruses encode rna helicases and chaperones, their in vitro activities and their roles in infected cells largely remain elusive. noroviruses are a diverse group of positive-strand rna viruses in the family caliciviridae and constitute a significant and potentially fatal threat to human health. here, we report that the protein ns3 encoded by human norovirus has both atp-dependent rna helicase activity that unwinds rna helices and atp-independent rna-chaperoning activity that can remodel structured rnas and facilitate strand annealing. moreover, ns3 can facilitate viral rna synthesis in vitro by norovirus polymerase. ns3 may therefore play an important role in norovirus rna replication. lastly, we demonstrate that the rna-remodeling activity of ns3 is inhibited by guanidine hydrochloride, an fda-approved compound, and, more importantly, that it reduces the replication of the norovirus replicon in cultured human cells. altogether, these findings are the first to demonstrate the presence of rna-remodeling activities encoded by caliciviridae and highlight the functional significance of ns3 in the noroviral life cycle. importance noroviruses are a diverse group of positive-strand rna viruses, which annually cause hundreds of millions of human infections and over 200,000 deaths worldwide. for rna viruses, cellular or virus-encoded rna helicases and/or chaperones have long been considered to play pivotal roles in viral life cycles. however, neither rna helicase nor chaperoning activity has been demonstrated to be associated with any norovirus-encoded proteins, and it is also unknown whether norovirus replication requires the participation of any viral or cellular rna helicases/chaperones. we found that a norovirus protein, ns3, not only has atp-dependent helicase activity, but also acts as an atp-independent rna chaperone. also, ns3 can facilitate in vitro viral rna synthesis, suggesting the important role of ns3 in norovirus replication. moreover, ns3 activities can be inhibited by an fda-approved compound, which also suppresses norovirus replicon replication in human cells, raising the possibility that ns3 could be a target for antinoroviral drug development.
WOS关键词EATON-LAMBERT SYNDROME ; NORWALK-LIKE VIRUSES ; NUCLEOSIDE TRIPHOSPHATASE ; BIOLOGICAL-ACTIVITIES ; REPLICATIVE HELICASE ; GUANIDINE COMPOUNDS ; PROTEIN 2C ; CELL-LINE ; POLIOVIRUS ; GENOME
WOS研究方向Virology
WOS类目Virology
语种英语
出版者AMER SOC MICROBIOLOGY
WOS记录号WOS:000424744800004
内容类型期刊论文
URI标识http://www.corc.org.cn/handle/1471x/2373337
专题武汉病毒研究所
通讯作者Zhou, Xi
作者单位1.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan, Hubei, Peoples R China
2.Wuhan Univ, Coll Life Sci, Wuhan, Hubei, Peoples R China
3.Univ Cambridge, Addenbrookes Hosp, Dept Pathol, Div Virol, Cambridge, England
4.Imperial Coll London, Dept Life Sci, London, England
推荐引用方式
GB/T 7714
Li, Teng-Feng,Hosmillo, Myra,Schwanke, Hella,et al. Human norovirus ns3 has rna helicase and chaperoning activities[J]. Journal of virology,2018,92(5):18.
APA Li, Teng-Feng.,Hosmillo, Myra.,Schwanke, Hella.,Shu, Ting.,Wang, Zhaowei.,...&Zhou, Xi.(2018).Human norovirus ns3 has rna helicase and chaperoning activities.Journal of virology,92(5),18.
MLA Li, Teng-Feng,et al."Human norovirus ns3 has rna helicase and chaperoning activities".Journal of virology 92.5(2018):18.
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