title: A large and intact viral particle penetrates the endoplasmic reticulum membrane to reach the cytosol.
abstract: Non-enveloped viruses penetrate host membranes to infect cells. A cell-based assay was used to probe the endoplasmic reticulum (ER)-to-cytosol membrane transport of the non-enveloped SV40. We found that, upon ER arrival, SV40 is released into the lumen and undergoes sequential disulfide bond disruptions to reach the cytosol. However, despite these ER-dependent conformational changes, SV40 crosses the ER membrane as a large and intact particle consisting of the VP1 coat, the internal components VP2, VP3, and the genome. This large particle subsequently disassembles in the cytosol. Mutant virus and inhibitor studies demonstrate VP3 and likely the viral genome, as well as cellular proteasome, control ER-to-cytosol transport. Our results identify the sequence of events, as well as virus and host components, that regulate ER membrane penetration. They also suggest that the ER membrane supports passage of a large particle, potentially through either a sizeable protein-conducting channel or the lipid bilayer.
authors: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors: Takamasa
authors: T
authors: Inoue
authors: Billy
authors: B
authors: Tsai
references: EMBO J. 2004 Jun 2;23(11):2206-15
references: 15152188
references: Structure. 1996 Feb 15;4(2):165-82
references: 8805523
references: Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):96-100
references: 8552683
references: J Virol. 2002 May;76(10):5156-66
references: 11967331
references: EMBO J. 2003 Sep 1;22(17):4346-55
references: 12941687
references: J Virol. 2009 Jan;83(1):37-46
references: 18945763
references: Mol Cell. 2005 Oct 28;20(2):289-300
references: 16246730
references: J Biol Chem. 1989 Feb 15;264(5):2665-71
references: 2464591
references: Nat Cell Biol. 2010 Jan;12(1):11-8; sup pp 1-12
references: 20023649
references: Mol Cell. 2006 Dec 28;24(6):955-66
references: 17189196
references: Annu Rev Cell Dev Biol. 1998;14:111-36
references: 9891780
references: Nature. 1991 Nov 28;354(6351):278-84
references: 1659663
references: Mol Biol Cell. 2008 Mar;19(3):877-84
references: 18094046
references: PLoS Pathog. 2009 Jun;5(6):e1000465
references: 19503604
references: J Virol. 1986 Dec;60(3):1098-106
references: 3023661
references: J Cell Biol. 2005 Jan 31;168(3):477-88
references: 15668298
references: Trends Microbiol. 2003 Aug;11(8):374-82
references: 12915095
references: Nature. 2007 Jul 26;448(7152):435-8
references: 17653186
references: Annu Rev Cell Dev Biol. 2007;23:23-43
references: 17456018
references: J Virol. 2007 Dec;81(23):12996-3004
references: 17881435
references: Cell. 2007 Nov 2;131(3):516-29
references: 17981119
references: Annu Rev Biochem. 2010;79:803-33
references: 20196649
references: EMBO J. 1998 Jun 15;17(12):3233-40
references: 9628860
references: J Virol. 2007 Apr;81(8):3778-85
references: 17267496
references: J Cell Biol. 1989 Dec;109(6 Pt 1):2721-9
references: 2556405
references: J Virol. 2010 Oct;84(19):9840-52
references: 20668088
references: EMBO J. 1998 Jun 15;17(12):3251-7
references: 9628862
references: J Virol. 2002 Sep;76(18):9368-77
references: 12186919
references: J Virol. 2006 Jul;80(13):6575-87
references: 16775344
references: J Virol. 2006 May;80(10):5086-91
references: 16641302
references: Trends Biochem Sci. 2003 Dec;28(12):639-45
references: 14659695
references: Nat Rev Mol Cell Biol. 2008 Dec;9(12):944-57
references: 19002207
references: J Cell Biol. 2006 Jun 19;173(6):853-9
references: 16785320
references: Nat Cell Biol. 2001 May;3(5):473-83
references: 11331875
references: J Virol. 1984 May;50(2):363-71
references: 6323736
references: Mol Biol Cell. 1995 Jun;6(6):675-83
references: 7579687