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J. Virol. doi:10.1128/JVI.01964-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The Full-Length Protein Encoded by Human Cytomegalovirus Gene UL117 Is Required for the Proper Maturation of Viral Replication Compartments

Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri 63110

^* To whom correspondence should be addressed. Email: dongyu{at}borcim.wustl.edu.

	Abstract

Previously two large-scale mutagenic analyses showed that mutations in human cytomegalovirus gene UL117 resulted in a defect in virus growth in fibroblasts. Early transcriptional analyses have revealed several mRNAs from the UL119-UL115 region; however, specific transcripts encoding UL117-related proteins have not been identified. In this study, we identified two novel transcripts arising from the UL117 gene locus, and we reported that the UL117 ORF encoded the full-length protein pUL117 (45 kDa) and the shorter isoform pUL117.5 (35 kDa) as the result of translation initiation at alternative in-frame ATGs. Both proteins were expressed with early kinetics, but pUL117 accumulated at a lower abundance relative to pUL117.5. During HCMV infection, both proteins predominantly localized to the nucleus, and the major fraction of pUL117 localized in viral nuclear replication compartments. We constructed mutant HCMV viruses in which the entire UL117 coding sequence was deleted or the expression of pUL117 was specifically abrogated. Growth of mutant viruses was significantly attenuated, indicating that pUL117 was required for efficient virus infection in fibroblasts. Cells infected with pUL117-deficient mutant virus accumulated representative viral immediate early proteins and early proteins normally. In the absence of pUL117, accumulation of replicating viral DNA was reduced no more than 2-fold in early times and was indistinguishable to wild-type at 72h post infection. Strikingly, there was a 12-24h delay in development of nuclear replication compartments and a marked delay in expression of late viral proteins. We conclude that pUL117 acts to promote the development of nuclear replication compartments to facilitate viral growth.