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Journal of Virology, May 2002, p. 4764-4772, Vol. 76, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.10.4764-4772.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Neither LAT nor Open Reading Frame P Mutations Increase Expression of Spliced or Intron-Containing ICP0 Transcripts in Mouse Ganglia Latently Infected with Herpes Simplex Virus

Shun-Hua Chen,^1,2* Lily Yeh Lee,^3,4 David A. Garber,^3, Priscilla A. Schaffer,^3,4, David M. Knipe,³ and Donald M. Coen^1*

Department of Biological Chemistry and Molecular Pharmacology,¹ Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115,³ Dana-Farber Cancer Institute, Boston, Massachusetts 02115,⁴ Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China²

Received 10 December 2001/ Accepted 12 February 2002

Latent infections by herpes simplex virus are characterized by repression of productive-cycle gene expression. Several hypotheses to explain this repression involve inhibition of expression of the immediate-early gene activator ICP0 during latency. To address these hypotheses, we developed quantitative reverse transcriptase-PCR assays that detected spliced and intron-containing ICP0 transcripts in mouse ganglia latently infected with wild-type virus. In these ganglia, the numbers of spliced ICP0 transcripts correlated better with the numbers of transcripts from the immediate-early gene encoding ICP4 than with those from the early gene encoding thymidine kinase. There were fewer spliced than intron-containing ICP0 transcripts on average, with considerable ganglion-to-ganglion variation. We then investigated whether ICP0 expression in latently infected ganglia is reduced by the latency-associated transcripts (LATs) and whether splicing of ICP0 transcripts is inhibited by the product of open reading frame (ORF) P. A LAT deletion mutation which essentially eliminates expression of the major LATs did not appreciably increase levels of ICP0 transcripts. LAT deletion mutants did, however, appear to express reduced levels of intron-containing ICP0 transcripts. ORF P mutations did not alter levels of ICP0 transcripts in a manner consistent with inhibition of ICP0 splicing by ORF P. Although these results argue against antisense inhibition of ICP0 expression by LATs or inhibition of ICP0 splicing by ORF P, they are consistent with the possibilities of a block between immediate-early and early gene expression and regulation of spliced versus intron-containing ICP0 transcripts in latently infected ganglia.

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* Corresponding author. Mailing address for Shun-Hua Chen: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, ROC. Phone: 886-6-2353535, ext. 5633. Fax: 886-6-2082705. E-mail: shunhua@mail.ncku.edu.tw. Mailing address for Donald M. Coen: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Ave., Boston, MA 02115. Phone: 617-432-1691. Fax: 617-432-3833. E-mail: Don_Coen@hms.harvard.edu.

Present address: Vaccine Research Center, Emory University, Atlanta, GA 30329.

Present address: Department of Medicine, Division of Infectious Diseases, Harvard Medical School at the Beth Israel Deaconess Medical Center, Boston, MA 02215.

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Journal of Virology, May 2002, p. 4764-4772, Vol. 76, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.10.4764-4772.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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