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Journal of Virology, October 2009, p. 10797-10807, Vol. 83, No. 20
0022-538X/09/$08.00+0     doi:10.1128/JVI.01093-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Human Cytomegalovirus Exploits ESCRT Machinery in the Process of Virion Maturation {triangledown}

Ritesh Tandon,1* David P. AuCoin,2 and Edward S. Mocarski1

Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322,1 Department of Microbiology and Immunology, 1664 N. Virginia Street, University of Nevada School of Medicine, Reno, Nevada 895572

Received 28 May 2009/ Accepted 21 July 2009

The endosomal sorting complex required for transport (ESCRT) machinery controls the incorporation of cargo into intraluminal vesicles of multivesicular bodies. This machinery is used during envelopment of many RNA viruses and some DNA viruses, including herpes simplex virus type 1. Other viruses mature independent of ESCRT components, instead relying on the intrinsic behavior of viral matrix and envelope proteins to drive envelopment. Human cytomegalovirus (HCMV) maturation has been reported to proceed independent of ESCRT components (A. Fraile-Ramos et al. Cell. Microbiol. 9:2955-2967, 2007). A virus complementation assay was used to evaluate the role of dominant-negative (DN) form of a key ESCRT ATPase, vacuolar protein sorting-4 (Vps4DN) in HCMV replication. Vps4DN specifically inhibited viral replication, whereas wild-type-Vps4 had no effect. In addition, a DN form of charged multivesicular body protein 1 (CHMP1DN) was found to inhibit HCMV. In contrast, DN tumor susceptibility gene-101 (Tsg101DN) did not impact viral replication despite the presence of a PTAP motif within pp150/ppUL32, an essential tegument protein involved in the last steps of viral maturation and release. Either Vps4DN or CHMP1DN blocked viral replication at a step after the accumulation of late viral proteins, suggesting that both are involved in maturation. Both Vps4A and CHMP1A localized in the vicinity of viral cytoplasmic assembly compartments, sites of viral maturation that develop in CMV-infected cells. Thus, ESCRT machinery is involved in the final steps of HCMV replication.

* Corresponding author. Mailing address: Emory Vaccine Center, 1462 Clifton Road, Atlanta, GA 30322. Phone: (404) 727-9456. Fax: (404) 712-9736. E-mail: rtandon{at}emory.edu

{triangledown} Published ahead of print on 29 July 2009.

Journal of Virology, October 2009, p. 10797-10807, Vol. 83, No. 20
0022-538X/09/$08.00+0     doi:10.1128/JVI.01093-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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