Human herpesvirus 1 protein US3 induces an inhibition of mitochondrial electron transport.
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.
Derakhshan
Mohammad
M
School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK.
Willcocks
Margaret M
MM
School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK.
Salako
Michael A
MA
School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK.
Kass
George E N
GEN
School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK.
Carter
Michael J
MJ
School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK.
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*
D014764:Viral Proteins; D013384:Succinate Cytochrome c Oxidoreductase; D017346:Protein Serine-Threonine Kinases; C095207:US3 protein, Human herpesvirus 1