Immunobiology and Host Response to HEV

Hepatitis E virus (HEV) causes acute self-limiting hepatitis in most cases and chronic infection in rare circumstances. It is believed to be noncytopathic, so immunologically mediated events should play important roles in its pathogenesis and infection outcomes. The anti-HEV antibody response was clarified when the major antigenic determinants on the ORF2 polypeptide were determined, which are located in its C-terminal portion. This subregion also forms the conformational neutralization epitopes. Robust anti-HEV immunoglobulin M (IgM) and IgG responses usually develop 3-4 weeks after infection in experimentally infected nonhuman primates. In humans, potent specific IgM and IgG responses occur in the very early phase of the disease and are critical in eliminating the virus, in concert with the innate and adaptive T-cell immune responses. They are also very valuable in the diagnosis of acute hepatitis E, when patients are tested for both anti-HEV IgM and IgG. The long-term persistence and protection of anti-HEV IgG provide the basis for estimating the prevalence of HEV infection and for the development of a hepatitis E vaccine. Although HEV has four genotypes, all the viral strains are considered to belong to a single serotype. It is becoming increasingly clear that the innate and adaptive T-cell immune responses play critical roles in the clearance of the virus. Potent and multispecific CD4⁺ and CD8⁺ T-cell responses to the ORF2 protein occur in patients with acute hepatitis E, and weaker HEV-specific CD4⁺ and CD8⁺ T-cell responses appear to be associated with chronic hepatitis E in immunocompromised individuals.