Cellular entry and uncoating of naked and quasi-enveloped human hepatoviruses

Elife. 2019 Feb 25;8:e43983. doi: 10.7554/eLife.43983.


Many 'non-enveloped' viruses, including hepatitis A virus (HAV), are released non-lytically from infected cells as infectious, quasi-enveloped virions cloaked in host membranes. Quasi-enveloped HAV (eHAV) mediates stealthy cell-to-cell spread within the liver, whereas stable naked virions shed in feces are optimized for environmental transmission. eHAV lacks virus-encoded surface proteins, and how it enters cells is unknown. We show both virion types enter by clathrin- and dynamin-dependent endocytosis, facilitated by integrin β1, and traffic through early and late endosomes. Uncoating of naked virions occurs in late endosomes, whereas eHAV undergoes ALIX-dependent trafficking to lysosomes where the quasi-envelope is enzymatically degraded and uncoating ensues coincident with breaching of endolysosomal membranes. Neither virion requires PLA2G16, a phospholipase essential for entry of other picornaviruses. Thus naked and quasi-enveloped virions enter via similar endocytic pathways, but uncoat in different compartments and release their genomes to the cytosol in a manner mechanistically distinct from other Picornaviridae.

Keywords: PLA2G16; endocytic trafficking; exosomes; extracellular vesicles; infectious disease; integrins; microbiology; picornavirus; virus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line
  • Endocytosis
  • Hepatitis A virus / physiology*
  • Hepatocytes / virology*
  • Humans
  • Lysosomes / virology
  • Virus Internalization*
  • Virus Uncoating*