Guanylate-Binding Protein 1 Inhibits Nuclear Delivery of Kaposi's Sarcoma-Associated Herpesvirus Virions by Disrupting Formation of Actin Filament
Zou, Zhe1; Meng, Zhihua1; Ma, Chao3; Liang, Deguang4; Sun, Rui4; Lan, Ke2,4
2017-08
Source PublicationJOURNAL OF VIROLOGY
ISSN0022-538X
Volume91Issue:16
Status已发表
DOI10.1128/JVI.00632-17
AbstractKaposi's sarcoma-associated herpesvirus (KSHV) is a typical gammaherpesvirus that establishes persistent lifelong infection in host cells. In order to establish successful infection, KSHV has evolved numerous immune evasion strategies to bypass or hijack the host immune system. However, host cells still produce immune cytokines abundantly during primary KSHV infection. Whether the immune effectors produced are able to inhibit viral infection and how KSHV successfully conquers these immune effectors remain largely unknown. The guanylate-binding protein 1 (GBP1) gene is an interferon-stimulated gene and exerts antiviral functions on several RNA viruses; however, its function in DNA virus infection is less well understood. In this study, we found that KSHV infection increases both the transcriptional and protein levels of GBP1 at the early stage of primary infection by activating the NF-kappa B pathway. The overexpression of GBP1 significantly inhibited KSHV infection, while the knockdown of GBP1 promoted KSHV infection. The GTPase activity and dimerization of GBP1 were demonstrated to be responsible for its anti-KSHV activity. Furthermore, we found that GBP1 inhibited the nuclear delivery of KSHV virions by disrupting the formation of actin filaments. Finally, we demonstrated that replication and transcription activator (RTA) promotes the degradation of GBP1 through a proteasome pathway. Taken together, these results provide a new understanding of the antiviral mechanism of GBP1, which possesses potent anti-KSHV activity, and suggest the critical role of RTA in the evasion of the innate immune response during primary infection by KSHV.
KeywordKSHV GBP1 GTPase activity actin filaments RTA Kaposi's sarcoma-associated herpesvirus
Indexed BySCI
Language英语
Funding ProjectNational Institutes of Health[1R01AI116442]
WOS Research AreaVirology
WOS SubjectVirology
WOS IDWOS:000406406600028
PublisherAMER SOC MICROBIOLOGY
WOS KeywordKAPPA-B ACTIVATION ; NUCLEOTIDE-BINDING ; ENDOTHELIAL-CELLS ; GTPASE ACTIVITY ; MICROTUBULE DYNAMICS ; MEDIATED DEGRADATION ; INDUCIBLE GTPASES ; GAMMA-INTERFERON ; INFECTION ; KSHV
Original Document TypeArticle
Corresponding AuthorLan, Ke
Citation statistics
Cited Times:11[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://kms.shanghaitech.edu.cn/handle/2MSLDSTB/2876
Collection生命科学与技术学院
生命科学与技术学院_博士生
Corresponding AuthorLan, Ke
Affiliation1.Shanghai Univ, Sch Life Sci, Shanghai, Peoples R China
2.Wuhan Univ, Coll Life Sci, State Key Lab Virol, Wuhan, Hubei, Peoples R China
3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
4.Shanghai Chinese Acad Sci, Key Lab Mol Virol & Immunol, Inst Pasteur, Shanghai, Peoples R China
Recommended Citation
GB/T 7714
Zou, Zhe,Meng, Zhihua,Ma, Chao,et al. Guanylate-Binding Protein 1 Inhibits Nuclear Delivery of Kaposi's Sarcoma-Associated Herpesvirus Virions by Disrupting Formation of Actin Filament[J]. JOURNAL OF VIROLOGY,2017,91(16).
APA Zou, Zhe,Meng, Zhihua,Ma, Chao,Liang, Deguang,Sun, Rui,&Lan, Ke.(2017).Guanylate-Binding Protein 1 Inhibits Nuclear Delivery of Kaposi's Sarcoma-Associated Herpesvirus Virions by Disrupting Formation of Actin Filament.JOURNAL OF VIROLOGY,91(16).
MLA Zou, Zhe,et al."Guanylate-Binding Protein 1 Inhibits Nuclear Delivery of Kaposi's Sarcoma-Associated Herpesvirus Virions by Disrupting Formation of Actin Filament".JOURNAL OF VIROLOGY 91.16(2017).
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