The Open Reading Frame 4 Region is Involved in Hepatitis E Virus Adaptation

The hepatitis E virus (HEV) is the cause of the liver disease hepatitis E. The HEV open reading frame 4 (ORF4) region functional implication in adaptive evolution remains to be elucidated. The parameters, including amino acid composition, structural annotation, function and protein-protein interaction, influence a protein’s process of adaptation. Therefore, in this chapter, various factors were comprehensively studied, using bioinformatics tools, which play a vital role in the evolutionary adaptation of ORF4. The composition of ORF4 revealed the presence of both disordered and ordered amino acid residues. The ORF4 evolution was shaped by pressures that led to the predominance of disorder-promoting amino acid residues, including Ala, Gly, Leu, Pro, Arg and Ser. Structure evaluation of ORF4 revealed the presence of both structured and unstructured regions. The putative binding motifs were predicted in ORF4, captivating its involvement in the regulation of varying cellular signaling processes. Furthermore, structure-based functional annotation of ORF4 revealed its susceptibility in binding to a wide range of ligands. As disordered proteins are targets for regulation, ORF4 contributes to cellular signaling processes through protein-protein interactions. The proposed study presented here is the first attempt to delineate the role of ORF4 in adaptive evolution.