Origin, antigenicity, and function of a secreted form of ORF2 in hepatitis E virus infection

Abstract

Significance Hepatitis E virus (HEV) is a main cause of acute hepatitis worldwide. Recent evidence suggests that HEV-infected cells release a secreted form of ORF2 protein (ORF2 S ) but its origin and function are unknown. Here we demonstrate that ORF2 S and ORF2 C (the actual capsid protein) are different translation products and that ORF2 S is not essential for the HEV life cycle but inhibits antibody-mediated neutralization of HEV. Our results have important implications for understanding the HEV replication cycle and immune evasion mechanisms. The identified internal start codon in this study is highly conserved in most HEV strains, suggesting that the production of ORF2 S is an evolutionary conserved function for HEV.