The Hepatitis E virus intraviral interactome

Scientific Reports
Andreas OstermanMaria G Vizoso-Pinto

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 dr...Continue Reading

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Citations

Mar 12, 2016·Journal of Hepatology·Yannick DebingJérôme Gouttenoire
Sep 23, 2016·Frontiers in Microbiology·Yuchen Nan, Yan-Jin Zhang
Nov 9, 2016·Virologica Sinica·Bing HeYi Zeng
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Aug 9, 2019·Viruses·Robert LeDesmaAlexander Ploss
Dec 1, 2018·Emerging Microbes & Infections·Kiyoshi HimmelsbachEberhard Hildt
Apr 22, 2019·Biochemical and Biophysical Research Communications·Han YinLeiliang Zhang
Feb 23, 2020·Journal of Proteome Research·Shayli Varasteh MoradiKirill Alexandrov

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Methods Mentioned

BETA
Y2H
two-hybrid
pull-down
microscale thermophoresis

Software Mentioned

GraphPad Prism
Monolith
LuMPIS

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