title: A chaperone-activated nonenveloped virus perforates the physiologically relevant endoplasmic reticulum membrane.
abstract: The nonenveloped polyomavirus (Py) traffics from the plasma membrane to the endoplasmic reticulum (ER), where it penetrates the ER membrane, allowing the viral genome to reach the nucleus to cause infection. The mechanism of membrane penetration for Py, and for other nonenveloped viruses, remains poorly characterized. We showed previously that the ER chaperone ERp29 alters the conformation of Py coat protein VP1, enabling the virus to interact with membranes. Here, we developed a membrane perforation assay and showed that the ERp29-activated Py perforates the physiologically relevant ER membrane, an event that likely initiates viral penetration. Biochemical analysis revealed that the internal protein VP2 is exposed in the activated viral particle. Accordingly, we demonstrate that VP2 binds to, integrates into, and perforates the ER membrane; the other internal protein, VP3, binds to and integrates into the ER membrane but is not sufficient for perforation. Our data thus link the activity of a cellular factor on a nonenveloped virus to the membrane perforation event and identify a viral component that mediates this process.
authors: Department of Cell and Developmental Biology, University of Michigan Medical School, 109 Zina Pitcher Place, Rm. 3043, Ann Arbor, MI 48109, USA.
authors: Emily K
authors: EK
authors: Rainey-Barger
authors: Brian
authors: B
authors: Magnuson
authors: Billy
authors: B
authors: Tsai
mesh_terms: D036022:Capsid Proteins / Q000032:analysis* / Q000502:physiology*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000821:virology*; D006360:Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry / Q000821:virology*; D011120:Polyomavirus / Q000502:physiology*; D053586:Virus Internalization
chemical_list: D036022:Capsid Proteins; C491738:ERP29 protein, human; D006360:Heat-Shock Proteins; C442543:VP2 protein, Polyomavirus