Hepatitis E virus ORF2 capsid protein P2 domain (HEV ORF2 P2)

The P2 domain, also known as the E2s domain, is the most surface-exposed region of the Hepatitis E virus (HEV) ORF2 capsid protein [8, 15]. It plays a critical role in the viral life cycle by mediating attachment to host cell receptors, such as heparan sulfate proteoglycans, which initiates viral entry [8, 12]. Structurally, the P2 domain forms the characteristic protrusions or spikes on the viral capsid and contains the primary neutralizing epitopes targeted by the host immune system [11, 15]. Because of its essential role in infection and high immunogenicity, the P2 domain is the central target for vaccine development, most notably the Hecolin (HEV 239) vaccine [1, 4, 11]. Beyond its structural function, the ORF2 protein is produced in multiple isoforms, including a secreted glycosylated form (ORF2s) that circulates in the blood of infected patients [3, 13]. This secreted form acts as an immunological decoy, binding to and neutralizing anti-HEV antibodies to facilitate viral persistence and immune evasion [7, 13]. Recent studies have also identified that the ORF2 protein can actively suppress the host's innate immune response by interacting with TANK-binding kinase 1 (TBK1) and interfering with the RIG-I signaling pathway, thereby dampening interferon production [9, 18, 20]. Consequently, the P2 domain is a multifaceted target involved in viral entry, immune modulation, and pathogenesis [10, 17].

Other names

E2s domainP2 domainProtruding domainORF2pHEV 239

Induction of neutralizing antibodies that block viral attachment and entry into host cells.