title: Nuclear envelope breakdown induced by herpes simplex virus type 1 involves the activity of viral fusion proteins.
abstract: Herpesvirus infection reorganizes components of the nuclear lamina usually without loss of integrity of the nuclear membranes. We report that wild-type HSV infection can cause dissolution of the nuclear envelope in transformed mouse embryonic fibroblasts that do not express torsinA. Nuclear envelope breakdown is accompanied by an eight-fold inhibition of virus replication. Breakdown of the membrane is much more limited during infection with viruses that lack the gB and gH genes, suggesting that breakdown involves factors that promote fusion at the nuclear membrane. Nuclear envelope breakdown is also inhibited during infection with virus that does not express UL34, but is enhanced when the US3 gene is deleted, suggesting that envelope breakdown may be enhanced by nuclear lamina disruption. Nuclear envelope breakdown cannot compensate for deletion of the UL34 gene suggesting that mixing of nuclear and cytoplasmic contents is insufficient to bypass loss of the normal nuclear egress pathway.
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Martina
authors.initials: M
authors.lastname: Maric
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Alison C
authors.initials: AC
authors.lastname: Haugo
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: William
authors.initials: W
authors.lastname: Dauer
authors.affiliation: Department of Microbiology and Immunology, Oregon Health Sciences University, Portland, OR 97201, USA.
authors.forename: David
authors.initials: D
authors.lastname: Johnson
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA. Electronic address: richard-roller@uiowa.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Roller
mesh_terms: D000818:Animals; D002460:Cell Line; D006561:Herpes Simplex / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism* / Q000821:virology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C491548:Dyt1 protein, mouse; D018832:Molecular Chaperones; D014759:Viral Envelope Proteins; C562160:glycoprotein B, human herpesvirus 1; C044200:glycoprotein H, herpes simplex virus type 1
keywords: Fusion; HSV-1; Nuclear envelope; UL34; US3; gB; gH