Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States; Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, United States
Olga González-López
Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States; Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, United States
Anshuman Das
Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, United States
Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, United States; Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, United States
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.
