Hepatitis E virus ORF2 capsid protein P-domain (HEV ORF2 P-domain)

The Hepatitis E virus (HEV) ORF2 capsid protein P-domain is the protruding structural element of the viral capsid, forming dimeric spikes that are critical for viral attachment and entry into host cells [1.2.1, 1.4.1]. It functions by binding to cellular receptors, such as heparan sulfate proteoglycans, to initiate the infection process [1.1.1, 1.2.4]. As the most exposed part of the naked virion, the P-domain contains the major neutralizing epitopes, making it the primary target for vaccine development and neutralizing antibody therapies [1.2.1, 1.3.2]. The only commercially available HEV vaccine, Hecolin, is based on a recombinant truncated ORF2 protein (p239) that includes this P-domain [1.2.1, 1.3.2]. However, the effectiveness of P-domain-targeted interventions is complicated by the existence of quasi-enveloped HEV particles in the blood, which utilize host membranes to shield the capsid from antibody-mediated neutralization [1.3.2, 1.4.1]. Beyond its structural role, the ORF2 protein has been shown to antagonize host antiviral responses, although this function is often associated with the full-length protein or other specific motifs [1.1.2, 1.3.3]. Understanding the structural dynamics of the P-domain is essential for developing next-generation vaccines and entry inhibitors that can overcome viral evasion mechanisms [1.4.1].

Other names

Hepatitis E virus ORF2 protruding domainHEV capsid P-domainHEV-CP P-domainORF2 P-domain

Neutralization of viral entry by blocking the interaction between the P-domain and host cell receptors [1.2.1, 1.4.1].