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Journal of Virology, October 2006, p. 9414-9423, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.00530-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Tissue-Specific Splicing of the Herpes Simplex Virus Type 1 Latency-Associated Transcript (LAT) Intron in LAT Transgenic Mice

Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida 32610-0266,¹ Division of Basic Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111,² F. I. Proctor Foundation, University of California Medical Center, San Francisco, California 94143-0944³

Received 14 March 2006/ Accepted 11 July 2006

To study the regulation of herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) expression and processing in the absence of other cis and trans viral functions, a transgenic mouse containing the region encompassing the LAT promoter (LAP1) and the LAT 5' exon through the 2.0-kb intron was created. LAT expression was detectable by reverse transcriptase PCR (RT-PCR) in a number of tissues, including the dorsal root ganglia (DRG), trigeminal ganglia (TG), brain, skin, liver, and kidney. However, when the accumulation of the 2.0-kb LAT intron was analyzed at the cellular level by in situ hybridization, little or no detectable accumulation was observed in the brain, spinal cord, kidney, or foot, although the 2.0-kb LAT intron was detected at high levels (over 90% of neurons) in the DRG and TG. Northern blot analysis detected the stable 2.0-kb LAT intron only in the sensory ganglia. When relative amounts of the spliced and unspliced LAT within the brain, liver, kidney, spinal cord, TG, and DRG were analyzed by real-time RT-PCR, splicing of the 2.0-kb LAT intron was significantly more efficient in the sensory ganglia than in other tissues. Finally, infection of both transgenic mice and nontransgenic littermates with HSV-1 revealed no differences in lytic replication, establishment of latency, or reactivation, suggesting that expression of the LAT transgene in trans has no significant effect on those functions. Taken together, these data indicate that the regulation of expression and processing of LAT RNA within the mouse is highly cell-type specific and occurs in the absence of other viral cis- and trans-acting factors.