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

Mohammad Derakhshan1, Margaret M Willcocks1, Michael A Salako1

  • 1School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK.

The Journal of General Virology
|July 19, 2006
PubMed

Insights

Human herpesvirus 1 (HHV-1) infection suppresses mitochondrial respiration by blocking the electron-transport chain. The viral protein US3 was identified as the key mediator of this HHV-1-induced mitochondrial dysfunction.

Area of Science:

  • Virology
  • Cellular Respiration
  • Mitochondrial Biology

Background:

  • Viruses can impact host cell mitochondria.
  • Previous research identified viral proteins that interact with mitochondria.
  • The specific mechanisms by which viruses inhibit mitochondrial function are not fully understood.

Purpose of the Study:

  • To investigate the effects of Human herpesvirus 1 (HHV-1) infection on mitochondrial respiration.
  • To identify the viral proteins responsible for HHV-1-induced mitochondrial dysfunction.
  • To determine the site of inhibition within the mitochondrial electron-transport chain.

Main Methods:

  • Assessing mitochondrial respiration in cells infected with various viruses, including HHV-1.
  • Analyzing the role of HHV-1 beta-phase proteins, specifically US3, in mitochondrial respiration.
  • Utilizing HHV-1 mutants lacking the US3 protein.
  • Investigating the integrity of the mitochondrial electron-transport chain.

Main Results:

  • HHV-1 and influenza virus reduced mitochondrial respiration; other tested viruses did not.
  • The inhibition of respiration was due to a block in the mitochondrial electron-transport chain.
  • Ectopic expression of HHV-1 protein US3 reproduced the inhibition of mitochondrial respiration.
  • An HHV-1 mutant lacking US3 failed to inhibit oxygen consumption.
  • The block in electron transport was localized between complexes II and III.

Conclusions:

  • HHV-1 infection suppresses mitochondrial respiration.
  • The viral protein US3 is the primary mediator of HHV-1-induced mitochondrial respiration suppression.
  • The mechanism involves a block in the mitochondrial electron-transport chain between complexes II and III.

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