title: Human Pirh2 is a novel inhibitor of prototype foamy virus replication.
abstract: Prototype foamy virus (PFV) is a member of the unconventional and nonpathogenic retroviruses. PFV causes lifelong chronic infections, which are partially attributable to a number of host cell factors that restrict viral replication. Herein, we identified human p53-induced RING-H2 protein (Pirh2) as a novel inhibitor of prototype foamy virus. Overexpression of Pirh2 decreased the replication of PFV, whereas knockdown of Pirh2 with specific siRNA increased PFV replication. Dual-luciferase assays and coimmunoprecipitation demonstrated that Pirh2 negatively influences the Tas-dependent transcriptional activation of the PFV long terminal repeat (LTR) and internal promoter (IP) by interacting with the transactivator Tas and down-regulating its expression. In addition, the viral inhibitory function of Pirh2 is N-terminal and RING domain dependent. Together, these results indicated that Pirh2 suppresses PFV replication by negatively impacting its transactivator Tas and the transcription of two viral promoters, which may contribute to the latency of PFV infection.
authors.affiliation: Pathogenic Organism and Infectious Diseases Research Institute, School of Basic Medical Sciences, Wuhan University, Donghu Road No. 185, Wuchang, Wuhan 430071, China. donglanlan.2006@163.com.|Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China. donglanlan.2006@163.com.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Dong
authors.affiliation: Pathogenic Organism and Infectious Diseases Research Institute, School of Basic Medical Sciences, Wuhan University, Donghu Road No. 185, Wuchang, Wuhan 430071, China. 2012203010043@whu.edu.cn.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Pathogenic Organism and Infectious Diseases Research Institute, School of Basic Medical Sciences, Wuhan University, Donghu Road No. 185, Wuchang, Wuhan 430071, China. wangzhihao@whu.edu.cn.
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Pathogenic Organism and Infectious Diseases Research Institute, School of Basic Medical Sciences, Wuhan University, Donghu Road No. 185, Wuchang, Wuhan 430071, China. yuanpeipei@whu.edu.cn.
authors.forename: Peipei
authors.initials: P
authors.lastname: Yuan
authors.affiliation: College of Life Sciences, Shanxi Normal University, Xi'an 710062, China. lizhi@snnu.edu.cn.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: College of Life Sciences, Shanxi Normal University, Xi'an 710062, China. sunyan@snnu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Pathogenic Organism and Infectious Diseases Research Institute, School of Basic Medical Sciences, Wuhan University, Donghu Road No. 185, Wuchang, Wuhan 430071, China. hansong@whu.edu.cn.
authors.forename: Song
authors.initials: S
authors.lastname: Han
authors.affiliation: Pathogenic Organism and Infectious Diseases Research Institute, School of Basic Medical Sciences, Wuhan University, Donghu Road No. 185, Wuchang, Wuhan 430071, China. yinjun@whu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.affiliation: Pathogenic Organism and Infectious Diseases Research Institute, School of Basic Medical Sciences, Wuhan University, Donghu Road No. 185, Wuchang, Wuhan 430071, China. pengbiwen@whu.edu.cn.
authors.forename: Biwen
authors.initials: B
authors.lastname: Peng
authors.affiliation: Pathogenic Organism and Infectious Diseases Research Institute, School of Basic Medical Sciences, Wuhan University, Donghu Road No. 185, Wuchang, Wuhan 430071, China. hexiaohua@whu.edu.cn.|Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China. hexiaohua@whu.edu.cn.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: He
authors.affiliation: Pathogenic Organism and Infectious Diseases Research Institute, School of Basic Medical Sciences, Wuhan University, Donghu Road No. 185, Wuchang, Wuhan 430071, China. liuwanhong@whu.edu.cn.|Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China. liuwanhong@whu.edu.cn.
authors.forename: Wanhong
authors.initials: W
authors.lastname: Liu
mesh_terms: D002460:Cell Line; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D006801:Humans; D053150:Simian foamy virus / Q000276:immunology* / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D017735:Virus Latency; D014779:Virus Replication / Q000187:drug effects*
chemical_list: C485369:RCHY1 protein, human; D044767:Ubiquitin-Protein Ligases
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