title: Human herpesvirus 1 protein US3 induces an inhibition of mitochondrial electron transport.
abstract: Previous studies have identified virus proteins that traffic to mitochondria and may affect mitochondrial function. Here, it is reported that Human herpesvirus 1 (HHV-1, herpes simplex virus 1) and influenza virus reduced mitochondrial respiration, whilst Measles virus, cytomegalovirus, coxsackievirus B4 and Feline calicivirus did not. The inhibition of total cellular respiration was caused by a block in the mitochondrial electron-transport chain. This effect occurred during beta-phase protein synthesis and the inhibition of mitochondrial respiration could be reproduced by ectopic expression of the beta-phase protein US3. An HHV-1 mutant lacking this protein failed to inhibit oxygen consumption in infected cells relative to controls. It was concluded that US3 was mediating the suppression of mitochondrial respiration following HHV-1 infection. The integrity of the electron-transport chain in HHV-1-infected cells was analysed further and the site of the block in electron transport was located between complexes II and III, a site previously shown to be affected by Poliovirus.
authors.affiliation: School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Derakhshan
authors.affiliation: School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Willcocks
authors.affiliation: School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Salako
authors.affiliation: School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK.
authors.forename: George E N
authors.initials: GEN
authors.lastname: Kass
authors.affiliation: School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Carter
mesh_terms: D000818:Animals; D017927:Calicivirus, Feline / Q000472:pathogenicity; D002415:Cats; D002460:Cell Line; D019069:Cell Respiration; D003587:Cytomegalovirus / Q000472:pathogenicity; D004285:Dogs; D004579:Electron Transport; D004770:Enterovirus / Q000472:pathogenicity; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity; D008459:Measles virus / Q000472:pathogenicity; D008928:Mitochondria / Q000378:metabolism*; D010101:Oxygen Consumption; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D013384:Succinate Cytochrome c Oxidoreductase / Q000037:antagonists & inhibitors*; D014764:Viral Proteins / Q000502:physiology*
chemical_list: D014764:Viral Proteins; D013384:Succinate Cytochrome c Oxidoreductase; D017346:Protein Serine-Threonine Kinases; C095207:US3 protein, Human herpesvirus 1