Immunobiology and Host Response to HEV

Hepatitis E virus (HEV) usually causes acute self-limiting hepatitis but sometimes leads to chronic infection in immunocompromised persons. HEV is not directly cytopathic. Immunologically mediated events after HEV infection are believed to play important roles in the pathogenesis and clearance of infection. The anti-HEV antibody responses have been largely clarified since the determination of major antigenic determinant of HEV, which is located in the C-terminal portion of ORF2. This major antigenic determinant 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. Testing anti-HEV IgM is valuable in the diagnosis of acute hepatitis E. 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 human 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.