Transcription of True Late (γ2) Cytomegalovirus Genes Requires UL92 Function That Is Conserved among Beta- and Gammaherpesviruses

• Type of Material: Article
• Authors: Shinya Omoto, Emory University; Edward S Mocarski, Emory University
• Language: English
• Date: 2014-01
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2014, American Society for Microbiology. All Rights Reserved.
• Final Published Version (URL): http://jvi.asm.org/content/88/1/120
• Title of Journal or Parent Work: Journal of Virology
• ISSN: 0022-538X
• Volume: 88
• Issue: 1
• Start Page: 120
• End Page: 130
• Grant/Funding Information: Public Health Service grant RO1 AI020211 funded this research.; S.O. is a visiting scholar at the Emory University supported by Shionogi & Co., Ltd., Japan.
• Research Categories: Biology, Microbiology; Health Sciences, Immunology; Biology, Virology

Abstract

Human cytomegalovirus-encoded UL92 plays an essential role in viral replication that has not been resolved. We show here that this gene controls the accumulation of true late (γ2) viral transcripts, a property shared with several other recently evaluated genes (UL79, UL87, UL91, and UL95) conserved among beta- and gammaherpesviruses. When the UL92 mutant virus was evaluated, function was fully complemented by either the natural protein or the homologous Rh127 protein from rhesus cytomegalovirus. N-terminal epitope-tagged UL92 protein is functional, follows complex early-late expression kinetics, and localizes in the nucleus within viral replication compartments. UL92 severely impacts the late (72-h postinfection) expression of nine genes encoding virion proteins (UL32, UL55, UL73, UL75, UL80, UL86, UL99, and UL115), as well as UL91 and itself, but does not influence the levels of UL44, UL82, or UL83 accumulation. Although viral DNA is made at normal levels, viral capsid accumulation in the nucleus is severely compromised in UL92 mutant virus-infected cells, and mature virions are not observed in the cytoplasm. Taken together, UL92 is a key regulator of late viral gene expression, apparently functioning with four other beta- or gammaherpesvirus gene products in a pattern that appears reminiscent of gene regulation in T4 DNA bacteriophage.