Publication Date:
2011-04-30
Description:
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 beta-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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Seo, Jun-Young -- Yaneva, Rakina -- Hinson, Ella R -- Cresswell, Peter -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 May 27;332(6033):1093-7. doi: 10.1126/science.1202007. Epub 2011 Apr 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520-8011, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21527675" target="_blank"〉PubMed〈/a〉
Keywords:
Actin Cytoskeleton/metabolism/ultrastructure
;
Adenosine Triphosphate/metabolism
;
Animals
;
COS Cells
;
Cell Line
;
Cells, Cultured
;
Cercopithecus aethiops
;
Cytomegalovirus/*metabolism/*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
;
Proteins/genetics/*metabolism
;
Recombinant Fusion Proteins/metabolism
;
Stress Fibers/ultrastructure
;
Transfection
;
Virus Replication
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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