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Human Cytomegalovirus Directly Induces the Antiviral Protein Viperin to Enhance Infectivity

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Science  28 Apr 2011:
1202007
DOI: 10.1126/science.1202007

Abstract

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 ER to the mitochondria. There, viperin interacted with the mitochondrial trifunctional protein that mediates β-oxidation of fatty acids to generate 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.