The HEV ORF1 polyprotein. A schematic illustration of the HEV ORF1 nonstructural polyprotein is shown, with the engineered N- and C-terminal tags. The predicted methyltransferase (MeT), papain-like cysteine protease (PCP), helicase (Hel) and RNA dependent RNA polymerase (RdRp) domains are shown, as is the GDD sequence that forms the RdRp active site. The numbers on top represent amino acids of the predicted domains numbered according to the ORF1 polyprotein sequence . The Y, proline-rich (Pro) and X regions with no predicted function are also shown. The tags engineered at the two ends include the N-terminal 6XHis tag of 45 amino acids (from vector pBBHis-2b) and a FLAG epitope of 12 amino acids as described in Materials and Methods. The entire recombinant ORF1 polyprotein engineered here is expected to be 1760 amino acids long, with a predicted mass of 191,806 Da.