title: SV40 VP2 and VP3 insertion into ER membranes is controlled by the capsid protein VP1: implications for DNA translocation out of the ER.
abstract: Nonenveloped viruses such as Simian Virus 40 (SV40) exploit established cellular pathways for internalization and transport to their site of penetration. By analyzing mutant SV40 genomes that do not express VP2 or VP3, we found that these structural proteins perform essential functions that are regulated by VP1. VP2 significantly enhanced SV40 particle association with the host cell, while VP3 functioned downstream. VP2 and VP3 both integrated posttranslationally into the endoplasmic reticulum (ER) membrane. Association with VP1 pentamers prevented their ER membrane integration, indicating that VP1 controls the function of VP2 and VP3 by directing their localization between the particle and the ER membrane. These findings suggest a model in which VP2 aids in cell binding. After capsid disassembly within the ER lumen, VP3, and perhaps VP2, oligomerizes and integrates into the ER membrane, potentially creating a viroporin that aids in viral DNA transport out of the ER.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, Massachusetts 01003, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Daniels
authors.forename: Nasser M
authors.initials: NM
authors.lastname: Rusan
authors.forename: Patricia
authors.initials: P
authors.lastname: Wadsworth
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Hebert
mesh_terms: D036022:Capsid Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D004279:DNA, Viral / Q000235:genetics*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D016679:Genome, Viral; D007425:Intracellular Membranes / Q000378:metabolism*; D008954:Models, Biological; D013539:Simian virus 40 / Q000235:genetics*; D014162:Transfection; D014178:Translocation, Genetic
chemical_list: D036022:Capsid Proteins; D004279:DNA, Viral; C062481:VP1 protein, polyomavirus; C085902:VP3 protein, Simian virus 40; C514199:Vp2 protein, simian virus 40