title: Varicella zoster virus infection of human fetal lung cells alters mitochondrial morphology.
abstract: Varicella zoster virus (VZV) is a ubiquitous alphaherpesvirus that establishes latency in ganglionic neurons throughout the neuraxis after primary infection. Here, we show that VZV infection induces a time-dependent significant change in mitochondrial morphology, an important indicator of cellular health, since mitochondria are involved in essential cellular functions. VZV immediate-early protein 63 (IE63) was detected in mitochondria-rich cellular fractions extracted from infected human fetal lung fibroblasts (HFL) by Western blotting. IE63 interacted with cytochrome c oxidase in bacterial 2-hybrid analyses. Confocal microscopy of VZV-infected HFL cells at multiple times after infection revealed the presence of IE63 in the nucleus, mitochondria, and cytoplasm. Our data provide the first evidence that VZV infection induces alterations in mitochondrial morphology, including fragmentation, which may be involved in cellular damage and/or death during virus infection.
authors.affiliation: Division of Endocrinology, University of Colorado School of Medicine, Aurora, 80045, CO, USA.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Keller
authors.affiliation: Department of Neurology, University of Colorado School of Medicine, 12700 E. 19th Avenue, Box B182, Aurora, 80045, CO, USA.
authors.forename: Hussain
authors.initials: H
authors.lastname: Badani
authors.affiliation: Division of Endocrinology, University of Colorado School of Medicine, Aurora, 80045, CO, USA.
authors.forename: P Mason
authors.initials: PM
authors.lastname: McClatchey
authors.affiliation: Department of Neurology, University of Colorado School of Medicine, 12700 E. 19th Avenue, Box B182, Aurora, 80045, CO, USA.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Baird
authors.affiliation: Department of Neurology, University of Colorado School of Medicine, 12700 E. 19th Avenue, Box B182, Aurora, 80045, CO, USA.
authors.forename: Jacqueline L
authors.initials: JL
authors.lastname: Bowlin
authors.affiliation: Department of Medicine, Denver VA Medical Center, Denver, 80220, CO, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Bouchard
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, and Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Guey-Chuen
authors.initials: GC
authors.lastname: Perng
authors.affiliation: Division of Endocrinology, University of Colorado School of Medicine, Aurora, 80045, CO, USA.|Department of Medicine, Denver VA Medical Center, Denver, 80220, CO, USA.
authors.forename: Jane E B
authors.initials: JE
authors.lastname: Reusch
authors.affiliation: Institut für Virologie, Freie Universität, Berlin, Germany.
authors.forename: Benedikt B
authors.initials: BB
authors.lastname: Kaufer
authors.affiliation: Department of Neurology, University of Colorado School of Medicine, 12700 E. 19th Avenue, Box B182, Aurora, 80045, CO, USA.|Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, 80045, CO, USA.
authors.forename: Don
authors.initials: D
authors.lastname: Gilden
authors.affiliation: Department of Biomolecular Structural Chemistry, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria.
authors.forename: Aamir
authors.initials: A
authors.lastname: Shahzad
authors.affiliation: Glasgow University Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, Scotland, UK.
authors.forename: Peter G E
authors.initials: PG
authors.lastname: Kennedy
authors.affiliation: Department of Neurology, University of Colorado School of Medicine, 12700 E. 19th Avenue, Box B182, Aurora, 80045, CO, USA. Randall.cohrs@ucdenver.edu.|Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, 80045, CO, USA. Randall.cohrs@ucdenver.edu.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Cohrs
mesh_terms: D016923:Cell Death / Q000235:genetics; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology; D003576:Electron Transport Complex IV / Q000235:genetics* / Q000378:metabolism; D005333:Fetus; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D014645:Herpesvirus 3, Human / Q000254:growth & development / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism; D008168:Lung / Q000166:cytology; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D017874:Immediate-Early Proteins; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; C485184:enhanced green fluorescent protein; C074551:immediate early protein 63, Human herpesvirus 3; D049452:Green Fluorescent Proteins; D003576:Electron Transport Complex IV
keywords: IE63; Mitochondria; Mitochondria morphology; Mitochondria swelling; Varicella zoster virus