title: Systematic identification of hepatitis E virus ORF2 interactome reveals that TMEM134 engages in ORF2-mediated NF-κB pathway.
abstract: Hepatitis E virus (HEV) is the causative agent of acute hepatitis E. Open reading frame 2 (ORF2) encodes the capsid protein of HEV, which is the main structural protein and may participate, together with the host factors, in viral entry and egress. However, it is still not clear which host proteins are involved in the interaction with ORF2 and what the functions of these ORF2-interacting proteins are. In this study, we have applied a split-ubiquitin yeast two-hybrid screening approach in combination with the pull-down and coimmunoprecipitation assays, identified and validated multiple interacting partners of ORF2 of genotype 1 and 4, which have diverse biological functions. Among these novel candidates that have not been previously reported, we have found that 20 of them are located in endoplasmic reticulum. TMEM134, which interacts and co-localizes with ORF2 in the endoplasmic reticulum, negatively regulates ORF2-mediated inhibition of the NF-κB signaling pathway. Our study for the first time has systematically mapped the ORF2 interactome in two genotypes of HEV, providing a new insight of understanding the virus-host interaction during the pathogenesis of HEV, and may offer potential therapeutic targets to intervene the HEV life cycle.
authors.affiliation: Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, Division of HIV/AIDS and Sexually Transmitted Virus Vaccines, National Institutes for Food and Drug Control, No. 2 Tiantanxili, Beijing 100050, China. Electronic address: tianyabin@nifdc.org.cn.
authors.forename: Yabin
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, Division of HIV/AIDS and Sexually Transmitted Virus Vaccines, National Institutes for Food and Drug Control, No. 2 Tiantanxili, Beijing 100050, China. Electronic address: huangweijin@nifdc.org.cn.
authors.forename: Weijin
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Surgery, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38015, USA. Electronic address: Jun.Yang2@stjude.org.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, Division of HIV/AIDS and Sexually Transmitted Virus Vaccines, National Institutes for Food and Drug Control, No. 2 Tiantanxili, Beijing 100050, China. Electronic address: zhihengw_bj@126.com.
authors.forename: Zhiheng
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Health Science Center, Hebei University, No. 342 Yuhuadonglu, Baoding 071000, China. Electronic address: ysgeng09@aliyun.com.
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, Division of HIV/AIDS and Sexually Transmitted Virus Vaccines, National Institutes for Food and Drug Control, No. 2 Tiantanxili, Beijing 100050, China. Electronic address: zhaochenyan@nifdc.org.cn.
authors.forename: Chenyan
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Bio-diagnosis, Institute of Basic Medical Sciences, 27, Taiping Road, Beijing 100850, China. Electronic address: zhangheqiu2004@126.com.
authors.forename: Heqiu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, Division of HIV/AIDS and Sexually Transmitted Virus Vaccines, National Institutes for Food and Drug Control, No. 2 Tiantanxili, Beijing 100050, China. Electronic address: wangyc@nifdc.org.cn.
authors.forename: Youchun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D002460:Cell Line; D019295:Computational Biology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D016751:Hepatitis E / Q000378:metabolism* / Q000821:virology*; D016752:Hepatitis E virus / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D058977:Molecular Sequence Annotation; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods; D060066:Protein Interaction Maps; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D016328:NF-kappa B; C400971:ORF2 protein, Hepatitis E virus; D014764:Viral Proteins
keywords: Hepatitis E virus; ORF2; Pull-down; Split-ubiquitin yeast two-hybrid screening; TMEM134