Conservation and variation of the hepatitis E virus ORF2 capsid protein

Hepatitis E virus (HEV) is one of the major pathogens causing acute viral hepatitis. The infectious particle consists of an RNA genome and capsid proteins. The 7.2 kb genome encodes three open reading frames (ORF) and ORF2 is translated into the capsid protein. The knowledge of structure and function of the ORF2 protein is essential for understanding the evolution and life cycle of HEV. However, biophysical research in this respect remains limited due to technical challenges. We have carried out a series of computational analysis on HEV ORF2. We have identified 144 conserved sites among the 660 amino acid (AA) residues. 43 models based on the previously proposed reference sequences and a cell culture adapted infectious clone were successfully built by 3D protein structure prediction and refinement. Structure alignment of domains revealed structural conservation of the S and M domains, but to a lesser extent of the P domain. Moreover, molecular docking has predicted distinct binding affinities of a monoclonal antibody towards ORF2 across different genotypes. Thus, we have expanded the information on ORF2 at both sequence and structure levels. These findings may help to better understand the evolution and life cycle of HEV, but also facilitate the development of genetically engineered vaccines or antibodies.