title: The Hepatitis E virus intraviral interactome.
abstract: Hepatitis E virus (HEV) is an emerging virus causing epidemic acute hepatitis in developing countries as well as sporadic cases in industrialized countries. The life cycle of HEV is still poorly understood and the lack of efficient cell culture systems and animal models are the principal limitations for a detailed study of the viral replication cycle. Here we exhaustively examine all possible intraviral protein-protein interactions (PPIs) of HEV by systematic Yeast two-hybrid (Y2H) and LuMPIS screens, providing a basis for studying the function of these proteins in the viral replication cycle. Key PPIs correlate with the already published HEV 3D structure. Furthermore, we report 20 novel PPIs including the homodimerization of the RNA dependent RNA polymerase (RdRp), the self-interaction of the papain like protease, and ORF3 interactions with the papain-like protease and putative replicase components: RdRp, methylase and helicase. Furthermore, we determined the dissociation constant (Kd) of ORF3 interactions with the viral helicase, papain-like protease and methylase, which suggest a regulatory function for ORF3 in orchestrating the formation of the replicase complex. These interactions may represent new targets for antiviral drugs.
authors.affiliation: Max von Pettenkofer-Institute, Department of Virology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Osterman
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Karlsruhe, Germany.|Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Stellberger
authors.affiliation: Max von Pettenkofer-Institute, Department of Virology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Gebhardt
authors.affiliation: Max von Pettenkofer-Institute, Department of Virology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Marisa
authors.initials: M
authors.lastname: Kurz
authors.affiliation: Institute for Informatics, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Friedel
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Karlsruhe, Germany.|Center for the Study of Biological Complexity, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Uetz
authors.affiliation: Max von Pettenkofer-Institute, Department of Virology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Nitschko
authors.affiliation: Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Baiker
authors.affiliation: Max von Pettenkofer-Institute, Department of Virology, Ludwig-Maximilians-University, Munich, Germany.|Instituto Superior de Investigaciones Biológicas (INSIBIO), CONICET-UNT, and Instituto de Fisiología, Facultad de Medicina, UNT. San Miguel de Tucumán, Argentina.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Vizoso-Pinto
mesh_terms: D016752:Hepatitis E virus / Q000378:metabolism*; D025941:Protein Interaction Mapping / Q000379:methods*; D020543:Proteome / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D020543:Proteome; D014764:Viral Proteins