A pathogenic picornavirus acquires an envelope by hijacking cellular membranes
By Zongdi Feng, L. Hensley, K. McKnight, F. Hu, V. Madden, L. Ping, S. Jeong, C. Walker, R. Lanford, S. Lemon. Nature, 2013
672 citations recorded by the source corpus.
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.
Subfields: Cardiology and Cardiovascular Medicine, Hepatology, Infectious Diseases
View Paper: https://www.semanticscholar.org/paper/477e0adedeb333f5b175369d433f02bbbd0671ac
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In Infectious Diseases
Citations in the corpus
- The biology, function, and biomedical applications of exosomes (2020, positive): “Although it remains unclear whether exosomes participate in viral immune evasion by limiting detection by neutralizing antibodies (96), they take part in augmenting viral entry into cells through the tetraspanins (transmembrane proteins) CD81 and CD9 present on exosomes, possibly by stabilizing the ”
- Fat(al) attraction: Picornaviruses Usurp Lipid Transfer at Membrane Contact Sites to Create Replication Organelles (2016, background): “The new virions are released into the extracellular environment upon host cell lysis, although growing evidence suggests that virions can also be secreted via nonlytic release prior to cell lysis and transmitted in vesicles containing multiple virions [8–12], similar to the mode observed previously ”