WDR5 Facilitates Human Cytomegalovirus Replication by Promoting Capsid Nuclear Egress

doi:10.1128/JVI.00207-18

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	WDR5 Facilitates Human Cytomegalovirus Replication by Promoting Capsid Nuclear Egress
	Zhao, Fei 2,3; Yang, Bo 2,3; Liu, Xi-Juan 2,3; Yao, Yongxuan 2,3; Jiang, Xuan 2,4; Wang, Xian-Zhang 2,3; Yang, Hong 2,3; Sun, Jin-Yan 2; Miao, Yun 5; Wang, Wei 6
刊名	JOURNAL OF VIROLOGY
	2018-05-01
卷号	92 期号:9 页码:19
关键词	human cytomegalovirus WDR5 IINMs capsid nuclear egress
ISSN号	0022-538X
DOI	10.1128/JVI.00207-18
英文摘要	WD repeat-containing protein 5 (WDR5) is essential for assembling the VISA-associated complex to induce a type I interferon antiviral response to Sendai virus infection. However, the roles of WDR5 in DNA virus infections are not well described. Here, we report that human cytomegalovirus exploits WDR5 to facilitate capsid nuclear egress. Overexpression of WDR5 in fibroblasts slightly enhanced the infectious virus yield. However, WDR5 knockdown dramatically reduced infectious virus titers with only a small decrease in viral genome replication or gene expression. Further investigation of late steps of viral replication found that WDR5 knockdown significantly impaired formation of the viral nuclear egress complex and induced substantially fewer infoldings of the inner nuclear membrane. In addition, fewer capsids were associated with these infoldings, and there were fewer capsids in the cytoplasm. Restoration of WDR5 partially reversed these effects. These results suggest that WDR5 knockdown impairs the nuclear egress of capsids, which in turn decreases virus titers. These findings reveal an important role for a host factor whose function(s) is usurped by a viral pathogen to promote efficient replication. Thus, WDR5 represents an interesting regulatory mechanism and a potential antiviral target. IMPORTANCE Human cytomegalovirus (HCMV) has a large (similar to 235-kb) genome with over 170 open reading frames and exploits numerous cellular factors to facilitate its replication. HCMV infection increases protein levels of WD repeat-containing protein 5 (WDR5) during infection, overexpression of WDR5 enhances viral replication, and knockdown of WDR5 dramatically attenuates viral replication. Our results indicate that WDR5 promotes the nuclear egress of viral capsids, the depletion of WDR5 resulting in a significant decrease in production of infectious virions. This is the first report that WDR5 favors HCMV, a DNA virus, replication and highlights a novel target for antiviral therapy.
资助项目	National Natural Science Foundation of China[81620108021] ; National Natural Science Foundation of China[81427801] ; National Natural Science Foundation of China[81271850] ; National Natural Science Foundation of China[81571355] ; Key Basic Research Project from MOST[2015CB755601] ; Sino-Africa Joint Research Center, Chinese Academy of Sciences[SAJC201605] ; Key Program of the Guangzhou Joint Healthcare Innovation Foundation[201704020229]
WOS研究方向	Virology
语种	英语
出版者	AMER SOC MICROBIOLOGY
WOS记录号	WOS:000430281200010
内容类型	期刊论文
源URL	[http://202.127.146.157/handle/2RYDP1HH/4884]
专题	中国科学院武汉植物园
通讯作者	Zhao, Fei; Luo, Min-Hua
作者单位	1.Univ Alabama Birmingham, Sch Med, Dept Pediat, Birmingham, AL USA 2.Wuhan Inst Virol, CAS Ctr Excellence Brain Sci & Intelligence Techn, State Key Lab Virol, Wuhan, Hubei, Peoples R China 3.Univ Chinese Acad Sci, Beijing, Peoples R China 4.Guangzhou Women & Children Med Ctr, Guangzhou, Guangdong, Peoples R China 5.Southern Med Univ, Nanfang Hosp, Organ Transplant Dept, Guangzhou, Guangdong, Peoples R China 6.Third Xiangya Hosp, Changsha, Hunan, Peoples R China 7.Huazhong Univ Sci & Technol, Britton Chance Ctr Biomed Photon, Wuhan Natl Lab Optoelect, Wuhan, Hubei, Peoples R China 8.Howard Univ, Coll Med, Dept Microbiol, Washington, DC USA 9.Univ Oslo, Oslo Univ Hosp, Dept Med Genet, Oslo, Norway 10.Virginia Commonwealth Univ, Sch Med, Dept Pediat, Richmond, VA USA
推荐引用方式 GB/T 7714	Zhao, Fei,Yang, Bo,Liu, Xi-Juan,et al. WDR5 Facilitates Human Cytomegalovirus Replication by Promoting Capsid Nuclear Egress[J]. JOURNAL OF VIROLOGY,2018,92(9):19.
APA	Zhao, Fei.,Yang, Bo.,Liu, Xi-Juan.,Yao, Yongxuan.,Jiang, Xuan.,...&Luo, Min-Hua.(2018).WDR5 Facilitates Human Cytomegalovirus Replication by Promoting Capsid Nuclear Egress.JOURNAL OF VIROLOGY,92(9),19.
MLA	Zhao, Fei,et al."WDR5 Facilitates Human Cytomegalovirus Replication by Promoting Capsid Nuclear Egress".JOURNAL OF VIROLOGY 92.9(2018):19.