Abstract

The broad aim of this proposal is to understand how several key genes of herpes simplex virus are regulated in the latent state. Using a number of recombinant viruses and establishing acute and latent infections in mouse ganglia, this proposal will the regulation of genes encoding the LAT transcript, and the genes for ICPO and ICP4 proteins. The procedures will emphasize the expression during latency, rather than in tissue culture. A part of this proposal is to understand how the LAT gene is transcribed, processed, and transported to the cytoplasm. A second part of this proposal is to determine the location of the promoter and the elements important for its transcription in neurons. An important set of promoters not transcribed during latency is the set of immediate-early promoters. The reason for their lack of transcription will be investigated. Finally, it is proposed to alter the expression of two important immediate-early genes during latency. Using promoters which are active in neurons, the genes for ICPO and ICP4 will be expressed and the phenotype of each recombinant virus during latency will be evaluated. These studies should facilitate an understanding of the mechanisms which are operating during a latent infection. The long term goal of these studies is to understand the molecular basis for the mechanisms which regulate the establishment, maintenance, and reactivation the latent state.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI028338-04
Application #
3142782
Study Section
Experimental Virology Study Section (EVR)
Project Start
1989-08-01
Project End
1994-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Berthomme, H; Thomas, J; Texier, P et al. (2001) Enhancer and long-term expression functions of herpes simplex virus type 1 latency-associated promoter are both located in the same region. J Virol 75:4386-93
Berthomme, H; Lokensgard, J; Yang, L et al. (2000) Evidence for a bidirectional element located downstream from the herpes simplex virus type 1 latency-associated promoter that increases its activity during latency. J Virol 74:3613-22
Lokensgard, J R; Berthomme, H; Feldman, L T (1997) The latency-associated promoter of herpes simplex virus type 1 requires a region downstream of the transcription start site for long-term expression during latency. J Virol 71:6714-9
Dobson, A T; Margolis, T P; Gomes, W A et al. (1995) In vivo deletion analysis of the herpes simplex virus type 1 latency-associated transcript promoter. J Virol 69:2264-70
Lokensgard, J R; Bloom, D C; Dobson, A T et al. (1994) Long-term promoter activity during herpes simplex virus latency. J Virol 68:7148-58
Farrell, M J; Margolis, T P; Gomes, W A et al. (1994) Effect of the transcription start region of the herpes simplex virus type 1 latency-associated transcript promoter on expression of productively infected neurons in vivo. J Virol 68:5337-43
Farrell, M J; Hill, J M; Margolis, T P et al. (1993) The herpes simplex virus type 1 reactivation function lies outside the latency-associated transcript open reading frame ORF-2. J Virol 67:3653-5
Farrell, M J; Dobson, A T; Feldman, L T (1991) Herpes simplex virus latency-associated transcript is a stable intron. Proc Natl Acad Sci U S A 88:790-4
Dobson, A T; Margolis, T P; Sedarati, F et al. (1990) A latent, nonpathogenic HSV-1-derived vector stably expresses beta-galactosidase in mouse neurons. Neuron 5:353-60