HEPATITIS E VIRUS ORF3 PROTEIN IS A HUB PROTEIN WITH REGULATORY FUNCTIONS

OSTERMAN, A.; STELLBERGER, T.; NITSCHKO, H.; UETZ, P.; BAIKER, A.; VIZOSO PINTO, M. G.

Mar del Plata

Congreso; 51 Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2015

SAIB

Hepatitis E Virus (HEV) is an emerging virus causing epidemic acute hepatitis in developing countries and with increasing importance in industrialized countries. HEV life cycle is still not well understood because of the lack of efficient cell cultures and small animal models. Therefore, the objective of this study was to exhaustively examine all possible intraviral protein-protein interactions (PPIs) to get a better insight into the function of HEV proteins using a systems biology approach. We used a systematic Yeast two-hybrid (Y2H) and LuMPIS (Luciferase detection MPB-Pull down Protein Interaction screen) to map the HEV genome-wide protein interaction map and provide 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. In addition, we present the Kd (dissociation constant) 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. Hence, these novel interactions may result in potential targets for new antivirals.