Peek-a-boo: membrane hijacking and the pathogenesis of viral hepatitis

• HAV and HEV are phylogenetically unrelated but possess similar dual lifestyles.
• Both circulate in vivo cloaked in membranes and hidden from antibodies, but are shed in feces as stable, non-enveloped virions.
• Enveloped and non-enveloped forms of HAV and HEV have similar infectivity in cell culture.
• Whether members of a viral family possess or lack an envelope is dependent on evolutionary forces.

Historically, animal viruses have been classified on the basis of the presence or absence of an envelope – an external lipid bilayer membrane typically carrying one or more viral glycoproteins. However, growing evidence indicates that some ‘non-enveloped’ viruses circulate in the blood of infected individuals enveloped in host-derived membranes that provide protection from neutralizing antibodies. In this opinion article, we discuss this novel strategy for virus survival and consider how it contributes to the pathogenesis of acute viral hepatitis. The acquisition of an envelope by non-enveloped viruses profoundly influences their interaction with the host at both the cellular and system level and challenges how we think about vaccine protection against these infections.