Format

Send to

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

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

Author information

1
Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States.
2
Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, United States.
3
Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, United States.

Abstract

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

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center