Cellular entry and uncoating of naked and quasi-enveloped human hepatoviruses
- University of North Carolina at 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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data tables have been provided for Figures 1-5 and Supplementary Figures S1-S5.
Article and author information
Author details
Efraín E Rivera-Serrano
Funding
National Institute of Allergy and Infectious Diseases (R01-AI103083)
- Stanley M Lemon
National Institute of Allergy and Infectious Diseases (R01-AI131685)
- Stanley M Lemon
National Institute of Allergy and Infectious Diseases (T32-AI007151)
- Efraín E Rivera-Serrano
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Wesley I Sundquist, University of Utah School of Medicine, United States
Version history
- Received: November 28, 2018
- Accepted: February 22, 2019
- Accepted Manuscript published: February 25, 2019 (version 1)
- Version of Record published: March 18, 2019 (version 2)
Copyright
© 2019, Rivera-Serrano et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Cellular entry and uncoating of naked and quasi-enveloped human hepatoviruses
eLife 8:e43983.
https://doi.org/10.7554/eLife.43983
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