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Journal of Virology, September 2004, p. 9750-9762, Vol. 78, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.18.9750-9762.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Human Cytomegalovirus UL76 Encodes a Novel Virion-Associated Protein That Is Able To Inhibit Viral Replication

Shang-Kwei Wang,1* Chang-Yih Duh,2 and Cheng-Wen Wu3

Department of Microbiology, Kaohsiung Medical University,1 Department of Marine Resources, National Sun Yat-sen University, Kaohsiung,2 National Health Research Institutes, Taipei, Taiwan3

Received 25 August 2003/ Accepted 17 May 2004

The human cytomegalovirus (HCMV) UL76 gene encodes a highly conserved herpesvirus protein, pUL76, which is able to modulate gene expression in either activation or repression. In this study, two specific transcripts were found to contain the reading frame of UL76, one a 4.5-kb and the other a 5.5-kb tricistronic mRNA encoding the UL76, UL77, and UL78 open reading frames. Both transcripts were expressed with true late kinetics, as revealed by data showing inhibition of production in the presence of phosphonoformic acid. Immediately after viral infection, pUL76 was found in the nuclear fraction and was detected in cells in the presence of the protein synthesis inhibitor cycloheximide. Subsequent virus particle purification and Western blot analysis revealed that two forms of pUL76 are associated within mature virions. The high-molecular-mass protein (H-pUL76) was verified as originating from a free form of pUL76 by cross-linking with an unknown protein(s). By performing a biochemical fractionation experiment with purified virions, we provide evidence that pUL76 and H-pUL76 are associated with the detergent-soluble (envelope) and -insoluble (tegument/capsid) fractions, respectively. Both results were consistent with the images exhibited by immunoelectron microscopy, which showed that the distribution of gold particles labeled by the anti-pUL76 antibody juxtaposed the compartments of the envelope and the tegument/capsid of the virion. Evidence indicated that expression of pUL76 at the immediate-early phase of the viral replication cycle leads to the inhibition of HCMV production. The viral constituent pUL76, with a dominant-negative effect on replication, may provide a novel mechanism for HCMV's resumption of latency.

* Corresponding author. Mailing address: 100 Shih-Chuan 1st Road, Department of Microbiology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Phone: 886-7-3121101 ext. 2150. Fax: 886-7-3218309. E-mail: skwang{at}cc.kmu.edu.tw.

Journal of Virology, September 2004, p. 9750-9762, Vol. 78, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.18.9750-9762.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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