Guanylate-Binding Protein 1 Inhibits Nuclear Delivery of Kaposi's Sarcoma-Associated Herpesvirus Virions by Disrupting Formation of Actin Filament

doi:10.1128/JVI.00632-17

	Guanylate-Binding Protein 1 Inhibits Nuclear Delivery of Kaposi's Sarcoma-Associated Herpesvirus Virions by Disrupting Formation of Actin Filament
	Zou, Zhe 1; Meng, Zhihua 1; Ma, Chao3 ; Liang, Deguang 4; Sun, Rui 4; Lan, Ke 2,4
	2017-08
发表期刊	JOURNAL OF VIROLOGY (IF:4.0[JCR-2023],4.0[5-Year])
ISSN	0022-538X
卷号	91 期号:16
发表状态	已发表
DOI	10.1128/JVI.00632-17
摘要	Kaposi'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.
关键词	KSHV GBP1 GTPase activity actin filaments RTA Kaposi's sarcoma-associated herpesvirus
收录类别	SCI
语种	英语
资助项目	National Institutes of Health[1R01AI116442]
WOS研究方向	Virology
WOS类目	Virology
WOS记录号	WOS:000406406600028
出版者	AMER SOC MICROBIOLOGY
WOS关键词	KAPPA-B ACTIVATION ; NUCLEOTIDE-BINDING ; ENDOTHELIAL-CELLS ; GTPASE ACTIVITY ; MICROTUBULE DYNAMICS ; MEDIATED DEGRADATION ; INDUCIBLE GTPASES ; GAMMA-INTERFERON ; INFECTION ; KSHV
原始文献类型	Article
通讯作者	Lan, Ke
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/2876
专题	生命科学与技术学院生命科学与技术学院_博士生
通讯作者	Lan, Ke
作者单位	1.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
推荐引用方式 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).