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Journal of Virology, October 2003, p. 11105-11113, Vol. 77, No. 20
0022-538X/03/$08.00+0 DOI: 10.1128/JVI.77.20.11105-11113.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Role of PACS-1 in Trafficking of Human Cytomegalovirus Glycoprotein B and Virus Production
Colin M. Crump,
Chien-Hui Hung, Laurel Thomas, Lei Wan, and Gary Thomas*
Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239
Received 21 April 2003/
Accepted 18 July 2003
The final envelopment of herpesviruses during assembly of new virions is thought to occur by the budding of core viral particles into a late secretory pathway organelle, the trans-Golgi network (TGN), or an associated endosomal compartment. Several herpesvirus envelope glycoproteins have been previously shown to localize to the TGN when expressed independently from other viral proteins. In at least some cases this TGN localization has been shown to be dependent on clusters of acidic residues within their cytoplasmic domains. Similar acidic cluster motifs are found in endogenous membrane proteins that also localize to the TGN. These acidic cluster motifs interact with PACS-1, a connector protein that is required for the trafficking of proteins containing such motifs from endosomes to the TGN. We show here that PACS-1 interacts with the cytoplasmic domain of the HCMV envelope glycoprotein B (gB) and that PACS-1 function is required for normal TGN localization of HCMV gB. Furthermore, inhibition of PACS-1 activity in infected cells leads to a decrease in HCMV titer, whereas an increase in expression of functional PACS-1 leads to an increase in HCMV titer, suggesting that PACS-1 is required for efficient production of HCMV.
* Corresponding author. Mailing address: Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239. Phone: (503) 494-6955. Fax: (503) 494-1218. E-mail: thomasg{at}ohsu.edu.
Present address: Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom.
Journal of Virology, October 2003, p. 11105-11113, Vol. 77, No. 20
0022-538X/03/$08.00+0 DOI: 10.1128/JVI.77.20.11105-11113.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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Copyright © 2003 by the American Society for Microbiology. All rights reserved.