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Journal of Virology, January 2008, p. 77-85, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01484-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Inhibition of Translation by a Short Element in the 5' Leader of the Herpes Simplex Virus 1 DNA Polymerase Transcript

Kevin F. Bryant and Donald M. Coen^*

Department of Biological Chemistry and Molecular Pharmacology and Committee on Virology, Harvard Medical School, Boston, Massachusetts 02115

Received 6 July 2007/ Accepted 17 October 2007

Many viruses regulate gene expression, both globally and specifically, to achieve maximal rates of replication. During herpes simplex virus 1 infection, translation of the DNA polymerase (Pol) catalytic subunit is inefficient relative to other proteins of the same temporal class (D. R. Yager, A. I. Marcy, and D. M. Coen., J. Virol. 64:2217-2225, 1990). To investigate the mechanisms involved in the inefficient translation of Pol and to determine whether this inefficient translation could affect viral replication, we performed a mutagenic analysis of the 5' end of the pol transcript. We found that a short sequence (55 bases) in the 5' leader of the transcript is both necessary and sufficient to inhibit translation in rabbit reticulocyte lysates and sufficient to inhibit reporter gene translation in transfected cells. RNase structure mapping experiments indicated that the inhibitory element adopts a structure that contains regions of a double-stranded nature, which may interfere with ribosomal loading and/or scanning. Pol accumulated to 2- to 3-fold-higher levels per mRNA in cells infected with a mutant virus containing a deletion of the 55-base inhibitory element than in cells infected with a control virus containing this element. Additionally, the mutant virus replicated less efficiently than the control virus. These results suggest that the inhibitory element regulates Pol translation during infection and that its inhibition of Pol translation is beneficial for viral replication.

Published ahead of print on 24 October 2007.

Present address: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115.