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Science 332 (6033): 1093-1097

Copyright © 2011 by the American Association for the Advancement of Science

Human Cytomegalovirus Directly Induces the Antiviral Protein Viperin to Enhance Infectivity

Jun-Young Seo, Rakina Yaneva, Ella R. Hinson, Peter Cresswell*

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 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.

Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520–8011, USA.

* To whom correspondence should be addressed. E-mail: peter.cresswell{at}yale.edu


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