Herc5 Attenuates Influenza A Virus by Catalyzing ISGylation of Viral NS1 Protein

	Herc5 Attenuates Influenza A Virus by Catalyzing ISGylation of Viral NS1 Protein
	Tang, YJ; Zhong, GX; Zhu, LH; Liu, X; Shan, YF; Feng, HP; Bu, ZG; Chen, HL; Wang, C
刊名	JOURNAL OF IMMUNOLOGY
	2010
卷号	184 期号:10 页码:5777-5790
通讯作者	Wang, C (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Mol Cell Biol Lab, Inst Biochem & Cell Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,hlchen1@yahoo.com ; cwang01@sibs.ac.cn
英文摘要	Ubiquitin-like protein ISG15, which is robustly induced by IFN or virus, is implicated to inhibit influenza A virus (IAV) in vivo. But the underlying mechanism still remains largely unknown. In this study, we report that Herc5 could catalyze conjugation of ISG15 onto IAV-NS1 protein, the critical virulence factor of IAV. This modification produces two more species, respectively mapped to IAV-NS1 at lysine 20, 41, 217, 219, and 108, 110, and 126. The ISGylated IAV-NS1 fails to form homodimers and inhibits relevant antiviral processes. Knockdown of Herc5 or ISG15 could partially alleviate IFN-beta-induced antiviral activities against IAV, whereas ectopic expression of the Herc5-mediated ISGylation system could distinctly potentiate IFN-beta-induced antiviral effects against IAV. Notably, IAV-NS1s of H5N1 avian IAVs display less ISGylation species than that of IAV-PR8/34 (human H1N1). Consistently, IAV-PR8/34 mutants deprived of IAV-NS1's ISGylation exhibit augmented viral propagation and virulence in both cultured cells and mice. Our study reports the first microbial target of ISGylation and uncovers the direct antiviral function and mechanism of this novel modification. The Journal of Immunology, 2010, 184: 5777-5790.
学科主题	Immunology
类目[WOS]	Immunology
关键词[WOS]	UBIQUITIN-LIKE PROTEIN ; INTERFERON REGULATORY FACTOR-3 ; INNATE ANTIVIRAL RESPONSE ; RNA-BINDING ; HUMAN-CELLS ; STIMULATED GENE-15 ; ISG15 MODIFICATION ; MESSENGER-RNAS ; SINDBIS VIRUS ; DOMAIN
收录类别	SCI
语种	英语
WOS记录号	WOS:000277530700041
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1062]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Tang, YJ,Zhong, GX,Zhu, LH,et al. Herc5 Attenuates Influenza A Virus by Catalyzing ISGylation of Viral NS1 Protein[J]. JOURNAL OF IMMUNOLOGY,2010,184(10):5777-5790.
APA	Tang, YJ.,Zhong, GX.,Zhu, LH.,Liu, X.,Shan, YF.,...&Wang, C.(2010).Herc5 Attenuates Influenza A Virus by Catalyzing ISGylation of Viral NS1 Protein.JOURNAL OF IMMUNOLOGY,184(10),5777-5790.
MLA	Tang, YJ,et al."Herc5 Attenuates Influenza A Virus by Catalyzing ISGylation of Viral NS1 Protein".JOURNAL OF IMMUNOLOGY 184.10(2010):5777-5790.