Hepatitis E virus capsid protein ORF2 (ORF2)

The Hepatitis E virus (HEV) capsid protein, encoded by the second open reading frame (ORF2), is the primary structural component of the HEV virion and a critical factor in the viral life cycle (UniProt P0C6Q4). It is a 72 kDa protein that assembles into an icosahedral shell, facilitating viral attachment to host cell receptors like heparan sulfate proteoglycans and subsequent entry via endocytosis (PubMed: 19828611). Beyond its structural role, ORF2 exists in multiple forms: the infectious capsid-incorporated form (ORF2i) and secreted non-infectious forms (ORF2s and ORF2c) that circulate in high concentrations in patient sera (PubMed: 29666251). These secreted forms are thought to act as immunological decoys, neutralizing host antibodies and allowing the virus to evade the immune system (PubMed: 29666253). ORF2 is the primary target for the Hecolin (HEV 239) vaccine, which uses a recombinant fragment of the protein to elicit protective neutralizing antibodies (WHO, 2024). Additionally, the detection of ORF2 antigen in clinical samples serves as a vital biomarker for diagnosing active infection and monitoring the efficacy of antiviral treatments (PubMed: 35574415). Recent research also suggests that ORF2 plays a role in antagonizing the host's innate immune response by interfering with RIG-I and TBK1 signaling pathways, making it a potential target for novel direct-acting antivirals (PubMed: 39893145).

Other names

HEV capsid proteinpORF2Major capsid proteinORF2iORF2sORF2c

Prevention of viral entry and attachment through the induction of neutralizing antibodies that bind to the capsid protein.