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Journal of Virology, October 2007, p. 10524-10531, Vol. 81, No. 19
0022-538X/07/$08.00+0     doi:10.1128/JVI.00123-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Herpes Simplex Virus Type 1 UL3 Transcript Starts within the UL3 Open Reading Frame and Encodes a 224-Amino-Acid Protein{triangledown}

Nancy S. Markovitz*

Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892

Received 18 January 2007/ Accepted 2 July 2007

Several different herpes simplex viruses (HSVs) and vectors are being explored as therapeutic products for use in the treatment of cancer and neurological disorders. The viral strain and the combination of mutant viral genes that ultimately may serve as a safe and optimal backbone for such products are still being explored. The large genome size and complexity of the viral life cycle make such determinations difficult, because the significance of differences between proposed products is difficult to evaluate. For example, we previously reported that two lineages of {gamma}34.5-deleted HSVs used in clinical studies differ from each other in the size of the UL3 protein expressed (M. J. Dambach et al., Mol. Ther. 13:891-898, 2006). Because the function of UL3 is not known and UL3 gene expression is poorly understood, the significance of such a difference cannot be predicted. Here, I begin to address the function of UL3 by investigating UL3 gene expression. I report that the transcript start site of UL3 mRNA isolated from HSV type 1 (HSV-1)-infected cells maps to a position downstream of the predicted translation start site. By constructing and characterizing the recombinant virus CB8116, which has a mutation in the first in-frame start codon of this UL3 transcript, I demonstrated that UL3 protein translation initiates at the second in-frame start codon of the UL3 open reading frame. This information adds to the body of basic knowledge of HSV-1 biology that forms the foundation for our current understanding of HSV-based products. Future research on HSV-1 biology will facilitate the rational design and evaluation of future generations of therapeutic viruses.

* Mailing address: Division of Cellular and Gene Therapies, HFM-725, Center for Biologics Evaluation and Research, 1401 Rockville Pike, Rockville, MD 20852. Phone: (301) 827-0623. Fax: (301) 827-0449. E-mail: nancy.markovitz{at}fda.hhs.gov

{triangledown} Published ahead of print on 11 July 2007.

Journal of Virology, October 2007, p. 10524-10531, Vol. 81, No. 19
0022-538X/07/$08.00+0     doi:10.1128/JVI.00123-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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