Human cytomegalovirus directly induces the antiviral protein viperin to enhance infectivity

Science. 2011 May 27;332(6033):1093-7. doi: 10.1126/science.1202007. Epub 2011 Apr 28.


Viperin is an interferon-inducible protein that is directly induced in cells by human cytomegalovirus (HCMV) infection. Why HCMV would induce viperin, which has antiviral activity, is unknown. We show that HCMV-induced viperin disrupts cellular metabolism to enhance the infectious process. Viperin interaction with the viral protein vMIA resulted in viperin relocalization from the endoplasmic reticulum to the mitochondria. There, viperin interacted with the mitochondrial trifunctional protein that mediates β-oxidation of fatty acids to generate adenosine triphosphate (ATP). This interaction with viperin, but not with a mutant lacking the viperin iron-sulfur cluster-binding motif, reduced cellular ATP generation, which resulted in actin cytoskeleton disruption and enhancement of infection. This function of viperin, which was previously attributed to vMIA, suggests that HCMV has coopted viperin to facilitate the infectious process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actin Cytoskeleton / ultrastructure
  • Adenosine Triphosphate / metabolism
  • Animals
  • COS Cells
  • Cell Line
  • Cells, Cultured
  • Chlorocebus aethiops
  • Cytomegalovirus / metabolism*
  • Cytomegalovirus / pathogenicity*
  • Endoplasmic Reticulum / metabolism
  • Fatty Acids / metabolism
  • Glycolysis
  • Humans
  • Hydrogen-Ion Concentration
  • Immediate-Early Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Mitochondria / metabolism
  • Mitochondrial Trifunctional Protein
  • Multienzyme Complexes / metabolism
  • Oxidation-Reduction
  • Oxidoreductases Acting on CH-CH Group Donors
  • Proteins / genetics
  • Proteins / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Stress Fibers / ultrastructure
  • Transfection
  • Virus Replication


  • Fatty Acids
  • Immediate-Early Proteins
  • Multienzyme Complexes
  • Proteins
  • Recombinant Fusion Proteins
  • Rsad2 protein, mouse
  • UL37 protein, Human herpesvirus 5
  • Adenosine Triphosphate
  • Oxidoreductases Acting on CH-CH Group Donors
  • RSAD2 protein, human
  • Mitochondrial Trifunctional Protein