Human herpesvirus 1 protein US3 induces an inhibition of mitochondrial electron transport

School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK.
Journal of General Virology (Impact Factor: 3.18). 09/2006; 87(Pt 8):2155-9. DOI: 10.1099/vir.0.81949-0
Source: PubMed

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.

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    • "The role of IAV in the cellular energy processes remains unclear. Mitochondrial O 2 consumption decreased in epithelial cells infected with influenza A/PR/8/34 (Derakhshan et al., 2006). The IAV protein PB1-F2 has been shown to partition with the mitochondrial inner membrane (Gibbs et al., 2003; Yamada et al., 2004). "
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    ABSTRACT: Inhibition of cellular respiration, oxidation of glutathione and induction of apoptosis have been reported in epithelial cells infected in vitro with influenza A virus (IAV). Here, the same biomarkers were investigated in vivo by assessing the lungs of BALB/c mice infected with IAV. Cellular respiration declined on day 3 and recovered on day 7 post-infection. For days 3-5, the rate (mean±SD) of respiration (µMO2min(-1)mg(-1)) in uninfected lungs was 0.103±0.021 (n=4) and in infected lungs was 0.076±0.025 (n=4, p=0.026). Relative cellular ATP (infected/uninfected) was 4.7 on day 2 and 1.07 on day 7. Intracellular caspase activity peaked on day 7. Cellular glutathione decreased by ≥10% on days 3-7. Lung pathology was prominent on day 3 and caspase-3 labeling was prominent on day 5. IAV infection was associated with suppression of cellular respiration, diminished glutathione, and induction of apoptosis. These functional biomarkers were associated with structural changes noted in infected mice.
    Virology 11/2013; 446(1-2):180-8. DOI:10.1016/j.virol.2013.07.034 · 3.32 Impact Factor
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    • "These reports suggest the special involvement of ANT2 in conditions of stress, not only in cancer cells but also in viral infection. In addition, some mitochondrial changes in HSV-infected cells have been reported [26,27]. Spherical morphological change of mitochondria was observed using intensified fluorescence digital imaging at an early point in infection [28]. "
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    ABSTRACT: The herpes simplex virus 1 (HSV-1) UL7 gene is highly conserved among herpesviridae. Since the construction of recombinant HSV-1 with a mutation in the UL7 gene has not been reported, the involvement of HSV-1 UL7 in viral replication has been unclear. In this study, we succeeded in generating a UL7 null HSV-1 mutant virus, MT102, and characterized it. Our results were as follows. (i) In Vero cells, MT102 was replication-competent, but formed smaller plaques and yielded 10- to 100-fold fewer progeny than the wild-type virus, depending on the multiplicity of infection. (ii) Using mass spectrometry-based proteomics technology, we identified a cellular mitochondrial protein, adenine nucleotide translocator 2 (ANT2), as a UL7-interacting partner. (iii) When ANT2 was transiently expressed in COS-7 cells infected with HSV-1, ANT2 was specifically co-precipitated with UL7. (iv) Cell fractionation experiments with HSV-1-infected cells detected the UL7 protein in both the mitochondrial and cytosolic fractions, whereas ANT2 was detected only in the mitochondrial fraction. These results indicate the importance of HSV-1 UL7's involvement in viral replication and demonstrate that it interacts with ANT2 in infected cells. The potential biological significance of the interaction between UL7 and ANT2 is discussed.
    Virology Journal 11/2008; 5(1):125. DOI:10.1186/1743-422X-5-125 · 2.18 Impact Factor
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    • "Changes in location are observed after infection by Human herpesvirus 1 (HHV-1) and Hepatitis B virus [53,54]. The mitochondrial respiratory chain is affected by simian virus 40 [55], Poliovirus [56], HHV-1 and influenza virus [57]. The present study now suggests for the first time that virus infection might also modulate the amounts of mitochondrial mRNAs. "
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