TY - JOUR TI - Cellular entry and uncoating of naked and quasi-enveloped human hepatoviruses AU - Rivera-Serrano, Efraín E AU - González-López, Olga AU - Das, Anshuman AU - Lemon, Stanley M A2 - Sundquist, Wesley I A2 - Akhmanova, Anna A2 - Votteler, Joerg A2 - Estes, Mary VL - 8 PY - 2019 DA - 2019/02/25 SP - e43983 C1 - eLife 2019;8:e43983 DO - 10.7554/eLife.43983 UR - https://doi.org/10.7554/eLife.43983 AB - 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. KW - integrins KW - picornavirus KW - extracellular vesicles KW - exosomes KW - endocytic trafficking KW - PLA2G16 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -