Human cytomegalovirus induces the expression of a cellular antiviral protein to enhance its replication

Claire Williams, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0SP

In this weeks Science, Seo et al. report on the intriguing finding that optimal human cytomegalovirus (HCMV) replication relies on the expression of the antiviral protein viperin (1). Although infection with HCMV is usually asymptomatic, infection in pregnant women and the immunocompromised can have serious consequences. Infection of cells with HCMV induces the expression of many antiviral proteins, the function of many of which is unknown. Amongst these proteins is viperin, an interferon-inducible antiviral protein with an iron-sulphur binding cluster.

This study showed that rather than localising to the endoplasmic reticulum of infected cells, HCMV infection causes viperin to localise to mitochondria. It is known that HCMV encodes a viral protein called viral mitochondrial inhibitor of apoptosis (vMIA) which also localises to the mitochondria. Indeed, microscopy studies and co-immunoprecipitation studies showed that vMIA interacts with viperin and is responsible for the subcellular targeting of viperin. The function of vMIA was thought to be to cause disruption of the actin cytoskeleton of HCMV infected cells, facilitating viral infection. However, in virally infected mouse cells lacking viperin, this actin cytoskeletal rearrangement did not occur, suggesting that it is viperin which is actually responsible for this effect. Studies into the mechanism of action of viperin revealed that the protein interacts with and inhibits a mitochondrial multienzyme complex involved in fatty acid β-oxidation. The end result of this interaction is a decrease in ATP production in HCMV infected cells, to levels sufficient to interfere with the cytoskeleton but not to induce apoptosis, thus facilitating efficient viral replication.

In summary, this paper shows that HCMV hijacks a cellular antiviral protein to promote its own replication via effects on the cellular cytoskeleton. Increased knowledge of how viruses interact with the host cell machinery increases the potential for novel antiviral therapeutics to be developed.


(1) Seo J-Y, Yaneva R, Hinson ER, Cresswell P. Human Cytomegalovirus Directly Induces the Antiviral Protein Viperin to Enhance Infectivity. Science 2011 May;332(6033):1093 -1097.
doi: 10.1126/science.1202007

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