Human herpesvirus 1 protein U sub(S)3 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 U sub(S)3. An HHV-1 mutant lacking this protein failed to inhibit oxygen consumption in infected cells relative to controls. It was concluded that U sub(S)3 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 an IIID, a site previously shown to be affected by Poliovirus.