The Mystery of the Extra "Envelope"

HAV Apart from H7N9, the big news last week was the report that Hepatitis A Virus cloaks itself in membranes hijacked from infected cells. This made quite a splash, and was widely reported in terms of viruses having historically been classified into one of two types – those with an outer lipid-containing envelope and those without. The new paper claims that that hepatitis A virus, a common cause of enterically-transmitted hepatitis, takes on characteristics of both types depending on whether it is in a host or in the environment.

Actually, the reporting around this paper is misleading in my opinion. This is not a true virus envelope in the classical sense (i.e. a structural component of the virus particle), but an example of virus subversion of cellular exosomes – a type of membrane-bounded vesicle involved in cell-to-cell communication. Some viruses form actin “comet tails” to enable them to move from cell to cell – we don’t call them actin-containing viruses (Subversion of the actin cytoskeleton during viral infection. (2011) Nature Reviews Microbiology 9: 427-439).

Interesting then, but maybe not so new after all.


A pathogenic picornavirus acquires an envelope by hijacking cellular membranes. Nature. 2013 Mar 31. doi: 10.1038/nature12029
Animal viruses are broadly categorized structurally by the presence or absence of an envelope composed of a lipid-bilayer membrane, attributes that profoundly affect stability, transmission and immune recognition. Among those lacking an envelope, the Picornaviridae are a large and diverse family of positive-strand RNA viruses that includes hepatitis A virus (HAV), an ancient human pathogen that remains a common cause of enterically transmitted hepatitis. HAV infects in a stealth-like manner and replicates efficiently in the liver. Virus-specific antibodies appear only after 3-4 weeks of infection, and typically herald its resolution. Although unexplained mechanistically, both anti-HAV antibody and inactivated whole-virus vaccines prevent disease when administered as late as 2 weeks after exposure, when virus replication is well established in the liver. Here we show that HAV released from cells is cloaked in host-derived membranes, thereby protecting the virion from antibody-mediated neutralization. These enveloped viruses (‘eHAV’) resemble exosomes, small vesicles that are increasingly recognized to be important in intercellular communications. They are fully infectious, sensitive to extraction with chloroform, and circulate in the blood of infected humans. Their biogenesis is dependent on host proteins associated with endosomal-sorting complexes required for transport (ESCRT), namely VPS4B and ALIX. Whereas the hijacking of membranes by HAV facilitates escape from neutralizing antibodies and probably promotes virus spread within the liver, anti-capsid antibodies restrict replication after infection with eHAV, suggesting a possible explanation for prophylaxis after exposure. Membrane hijacking by HAV blurs the classic distinction between ‘enveloped’ and ‘non-enveloped’ viruses and has broad implications for mechanisms of viral egress from infected cells as well as host immune responses.

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One Response to The Mystery of the Extra "Envelope"

  1. John Carter says:

    In 1981, foot and mouth disease virus (another picornavirus) was reported to be released from cells by exocytosis:

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