Hepatitis E virus egress and beyond - the manifold roles of the viral ORF3 protein

Although the hepatitis E virus represents an uprising threat to the global community by representing the commonest cause of an acute viral hepatitis worldwide, its life cycle is grossly understudied. Albeit HEV is a non-enveloped virus, its progeny is released as quasi-enveloped virions. Thus, the responsible accessory protein pORF3 gained rising attention in the past years. It mediates viral release via the exosomal route by targeting the viral capsid to the endosomal system, more precisely to multivesicular bodies. As this is followed by quasi-envelopment, pORF3 may in terms represent a substitute to a conventional envelope protein. This feature proofs to be rather unique with respect to other enteric viruses, although the protein's role in the viral life cycle seems to reach far beyond simply maintaining release of progeny viruses. How pORF3 affects viral morphogenesis, how it mediates efficient viral release and how it supports viral spread is summarised in this microreview. With this, we aim to shed light on functions of pORF3 to gain further insights in still enigmatic aspects of the HEV life cycle. Take Aways HEV is released as exosome via multivesicular bodies Viral pORF3 mediates release via endosomal complexes required for transport pORF3 modulates various cellular processes in infected cells Elucidation of pORF3-related processes imply novel clinical strategies