A pathogenic picornavirus acquires an envelope by hijacking cellular membranes

Zongdi Feng, Lucinda Hensley, Kevin L. McKnight, Fengyu Hu, Victoria Madden, Lifang Ping, Sook Hyang Jeong, Christopher Walker, Robert E. Lanford, Stanley M. Lemon

Research output: Contribution to journalArticle

291 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)367-371
Number of pages5
JournalNature
Volume496
Issue number7445
DOIs
StatePublished - 18 Apr 2013

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Picornaviridae
Hepatitis A virus
Viruses
Membranes
Liver
Endosomal Sorting Complexes Required for Transport
Hepatitis A Antibodies
Exosomes
Antibodies
Capsid
RNA Viruses
Lipid Bilayers
Virus Replication
Chloroform
Infection
Neutralizing Antibodies
Virion
Hepatitis
Anti-Idiotypic Antibodies
Vaccines

Cite this

Feng, Z., Hensley, L., McKnight, K. L., Hu, F., Madden, V., Ping, L., ... Lemon, S. M. (2013). A pathogenic picornavirus acquires an envelope by hijacking cellular membranes. Nature, 496(7445), 367-371. https://doi.org/10.1038/nature12029
Feng, Zongdi ; Hensley, Lucinda ; McKnight, Kevin L. ; Hu, Fengyu ; Madden, Victoria ; Ping, Lifang ; Jeong, Sook Hyang ; Walker, Christopher ; Lanford, Robert E. ; Lemon, Stanley M. / A pathogenic picornavirus acquires an envelope by hijacking cellular membranes. In: Nature. 2013 ; Vol. 496, No. 7445. pp. 367-371.
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Feng, Z, Hensley, L, McKnight, KL, Hu, F, Madden, V, Ping, L, Jeong, SH, Walker, C, Lanford, RE & Lemon, SM 2013, 'A pathogenic picornavirus acquires an envelope by hijacking cellular membranes', Nature, vol. 496, no. 7445, pp. 367-371. https://doi.org/10.1038/nature12029

A pathogenic picornavirus acquires an envelope by hijacking cellular membranes. / Feng, Zongdi; Hensley, Lucinda; McKnight, Kevin L.; Hu, Fengyu; Madden, Victoria; Ping, Lifang; Jeong, Sook Hyang; Walker, Christopher; Lanford, Robert E.; Lemon, Stanley M.

In: Nature, Vol. 496, No. 7445, 18.04.2013, p. 367-371.

Research output: Contribution to journalArticle

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Feng Z, Hensley L, McKnight KL, Hu F, Madden V, Ping L et al. A pathogenic picornavirus acquires an envelope by hijacking cellular membranes. Nature. 2013 Apr 18;496(7445):367-371. https://doi.org/10.1038/nature12029