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18 - Early CMV gene expression and function

from Part II - Basic virology and viral gene effects on host cell functions: betaherpesviruses

Published online by Cambridge University Press:  24 December 2009

Elizabeth A. White
Affiliation:
Department of Cellular and Molecular Medicine and Center for Molecular Genetics, University of California, San Diego, La Jolla, CA, USA
Deborah H. Spector
Affiliation:
Department of Cellular and Molecular Medicine and Center for Molecular Genetics, University of California, San Diego, La Jolla, CA, USA
Ann Arvin
Affiliation:
Stanford University, California
Gabriella Campadelli-Fiume
Affiliation:
Università degli Studi, Bologna, Italy
Edward Mocarski
Affiliation:
Emory University, Atlanta
Patrick S. Moore
Affiliation:
University of Pittsburgh
Bernard Roizman
Affiliation:
University of Chicago
Richard Whitley
Affiliation:
University of Alabama, Birmingham
Koichi Yamanishi
Affiliation:
University of Osaka, Japan
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Summary

Introduction

Viral early genes are defined by two criteria: they require prior de novo synthesis of viral immediate-early (IE) and cellular proteins for their transcription, and this expression is insensitive to inhibitors of viral DNA synthesis such as phosphonoformate, ganciclovir, cidofovir, and phosphonoacetate. Close inspection of the kinetics of synthesis of this class of genes reveals multiple subgroups (for review, see Fortunato and Spector, 1999). The earliest of the early gene transcripts appear and accumulate to their highest levels by 8 hours postinfection (h p.i.) (e.g., the HCMV 2.2 kb family of transcripts – UL112–113), while the latest of the early transcripts cannot be detected until just prior to the onset of viral DNA replication (e.g., the HCMV 2.7 kb major early transcript – β2.7 or TRL4) and accumulate to highest levels much later during infection when viral DNA replication is allowed to proceed. (Mocarski and Courcelle, 2001) Levels of a third subgroup increase at late times (e.g., the abundant HCMV 1.2 kb RNA – TRL7) and are partially blocked by inhibitors of viral DNA synthesis. This subgroup may be further divided into genes that are referred to as early–late or leaky–late.

This review will describe the viral factors and cellular environment required for the expression of the viral early genes, the function of the early genes with respect to viral replication, and the subversion of host cellular processes and modulation of host immune responses that are associated with the expression of these genes.

Type
Chapter
Information
Human Herpesviruses
Biology, Therapy, and Immunoprophylaxis
, pp. 264 - 294
Publisher: Cambridge University Press
Print publication year: 2007

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