Functional Roles of the Human Cytomegalovirus Essential IE86 Protein
The IE86 protein of human cytomegalovirus (HCMV) is unique among viral and cellular proteins because it negatively autoregulates its own expression, activates the viral early and late promoters, and both activates and inhibits cellular promoters. It promo
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Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Mapping the Functional Domains of the IE86 Protein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Autoregulation of the MIE Promoter. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Transcription from Viral and Cellular Promoters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Viral Promoters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E2F Promoters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . NFκ-B Promoters. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cell Cycle Progression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Abstract The IE86 protein of human cytomegalovirus (HCMV) is unique among viral and cellular proteins because it negatively autoregulates its own expression, activates the viral early and late promoters, and both activates and inhibits cellular promoters. It promotes cell cycle progression from Go/G1 to G1/S and arrests cell cycle progression at the G1/S interface or at G2/Μ. The IE86 protein is essential because it creates a cellular environment favorable for viral replication. The multiple functions of the IE86 protein during the replication of HCMV are reviewed.
Introduction Human cytomegalovirus (HCMV) infection in utero is the leading infectious cause of birth defects that cause developmental disabilities. Infection of immunocompromised individuals can result in retinitis, pneumonitis, hepatitis, and gastroenteritis. There is no vaccine for HCMV, and the available antiviral therapies are fraught with M.F. Stinski Department of Microbiology, Interdisciplinary Program in Molecular Biology, University of Iowa, Iowa City, IA 52242, USA [email protected] T.E. Shenk and M.F. Stinski (eds.), Human Cytomegalovirus. Current Topics in Microbiology and Immunology 325. © Springer-Verlag Berlin Heidelberg 2008
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limited efficacy and high rates of adverse affects. Investigations of the essential proteins for HCMV replication may lead to novel antiviral strategies. This chapter will focus on the immediate early two gene (IE2) of HCMV, which encodes the essential multifunctional IE protein designated IE86. The IE2 gene is in a region of the viral DNA referred to as the major immediate early (MIE) gene locus. Transcription from the MIE gene locus does not require de novo
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