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

ELife
Efraín E Rivera-SerranoStanley M Lemon

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.

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Citations

Jun 4, 2019·Viruses·Vincent R GrazianoCraig B Wilen
Aug 2, 2019·Future Microbiology·Xingjian WenAnchun Cheng
Sep 25, 2019·Viruses·Xin Yin, Zongdi Feng
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Jul 17, 2021·Annual Review of Cell and Developmental Biology·Adeline KervielNihal Altan-Bonnet

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Datasets Mentioned

BETA
KP879216.1
KP879217.1

Methods Mentioned

BETA
fluorescence microscopy
transfections
GTPases
confocal microscopy
PCR
transfection
electrophoresis
Infrared Imaging

Software Mentioned

GraphPad Prism
Lalistat
Just Another Colocalisation Plugin ( JACoP )
ImageJ

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