Hepatitis E virus: from innate sensing to adaptive immune responses

Hepatitis E virus (HEV) infections are a major cause of acute viral hepatitis in humans worldwide. In immunocompetent individuals, the majority of HEV infections remain asymptomatic and lead to spontaneous clearance of the virus, and only a minority of individuals with infection (5-16%) experience symptoms of acute viral hepatitis. However, HEV infections can cause up to 30% mortality in pregnant women, become chronic in immunocompromised patients and cause extrahepatic manifestations. A growing body of evidence suggests that the host immune response to infection with different HEV genotypes is a critical determinant of distinct HEV infection outcomes. In this Review, we summarize key components of the innate and adaptive immune responses to HEV, including the underlying immunological mechanisms of HEV associated with acute and chronic liver failure and interactions between T cell and B cell responses. In addition, we discuss the current status of vaccines against HEV and raise outstanding questions regarding the immune responses induced by HEV and treatment of the disease, highlighting areas for future investigation. Many aspects of the biology and pathogenesis of hepatitis E virus (HEV) infection remain underexplored. In this Review, Steinmann and colleagues summarize the role of the innate and adaptive immune systems in HEV infection. The severity of hepatitis E virus (HEV) infection varies: for example, it is self-limiting in most immunocompetent individuals but can be fatal in pregnant women and lead to chronicity in immunocompromised individuals.A growing body of evidence suggests that the host immune response to infection with different HEV genotypes is a critical determinant of the distinct outcomes of HEV infection.HEV has developed strategies to evade and disrupt innate immune signalling by antagonizing interferon induction and signalling.T cell immunity is of paramount importance in the resolution of HEV infections.B cell immunity and antibody responses can provide sterilizing immunity and long-lasting protection against HEV re-infection.Active and passive immunization seem to effectively prevent severe acute hepatitis E in most cases.