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Journal of Virology, October 2006, p. 9730-9740, Vol. 80, No. 19
0022-538X/06/$08.00+0 doi:10.1128/JVI.00246-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine,1 UCLA Molecular Biology Interdepartmental Ph.D. Program,2 UCLA School of Dentistry,3 AIDS Institute,4 Jonsson Comprehensive Cancer Center,5 California Nano Systems Institute, University of California, Los Angeles, California 90095,6 Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China7
Received 2 February 2006/ Accepted 11 July 2006
Lytic replication of the tumor-associated human gammaherpesviruses Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus has important implications in pathogenesis and tumorigenesis. Herpesvirus lytic genes have been temporally classified as exhibiting immediate-early (IE), early, and late expression kinetics. Though the regulation of IE and early gene expression has been studied extensively, very little is known regarding the regulation of late gene expression. Late genes, which primarily encode virion structural proteins, require viral DNA replication for their expression. We have identified a murine gammaherpesvirus 68 (MHV-68) early lytic gene, ORF18, essential for viral replication. ORF18 is conserved in both beta- and gammaherpesviruses. By generating an MHV-68 ORF18-null virus, we characterized the stage of the virus lytic cascade that requires the function of ORF18. Gene expression profiling and quantitation of viral DNA synthesis of the ORF18-null virus revealed that the expression of early genes and viral DNA replication were not affected; however, the transcription of late genes was abolished. Hence, we have identified a gammaherpesvirus-encoded factor essential for the expression of late genes independently of viral DNA synthesis.
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