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Journal of Virology, September 2001, p. 8166-8172, Vol. 75, No. 17
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.17.8166-8172.2001

The 2.2-Kilobase Latency-Associated Transcript of Herpes Simplex Virus Type 2 Does Not Modulate Viral Replication, Reactivation, or Establishment of Latency in Transgenic Mice

Kening Wang,1,* Lesley Pesnicak,1 Elizabeth Guancial,1 Philip R. Krause,2 and Stephen E. Straus1

Medical Virology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases,1 and Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration,2 Bethesda, Maryland 20892

Received 17 January 2001/Accepted 18 May 2001

To better understand the mechanisms responsible for the observed effects of deletions in the promoter region of the latency-associated transcript (LAT) gene in impairing herpes simplex virus (HSV) reactivation, we generated mice transgenic for a 5.5-kb HSV type 2 (HSV-2) genomic fragment spanning the major LAT, along with the LAT promoter and flanking regions, in the C57BL/6 background. The mice expressed abundant 2.2-kb major LATs in trigeminal ganglia (TG) and other tissues. The effects of the transgene on HSV-2 infection, latency, and reactivation were assessed. When infected with wild-type (WT) HSV-2 or its LAT promoter deletion (LAT-) mutant, primary lung fibroblast lines established from normal C57BL/6 and transgenic mice supported virus growth equally well. The replication of these viruses in the mouse eye and their spread to TG and brains were similar. The quantities of latent viral DNA in TG of transgenic and normal mice, as determined by real-time PCR, were comparable. UV light-induced reactivation of the LAT- mutant from transgenic mice (0 to 7%) was no more frequent than that from normal mice (0 to 14%), while WT virus was reactivated from 13 to 54% of normal mice and 22 to 54% of transgenic mice. The cumulative data indicate that, when expressed transgenically, the HSV-2 major LAT cannot influence HSV-2 infection or latency and cannot complement the defect in reactivation of the LAT- mutant. These results imply that the phenotype of reduced reactivation associated with the LAT- mutant is related to a function encoded in the LAT promoter but not to the major LAT itself.

* Corresponding author. Mailing address: LCI/NIAID/NIH, 10 Center Dr., Rm. 11N228, Bethesda, MD 20892-1888. Phone: (301) 496-7895. Fax: (301) 496-7383. E-mail: kwang{at}niaid.nih.gov.

Journal of Virology, September 2001, p. 8166-8172, Vol. 75, No. 17
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.17.8166-8172.2001


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