Abstract

A series of variants of HSV which have altered patterns of pathogenesis in experimental animal systems have been identified. Examples include: 1) HSV-I and II intertypic recombinants (RE6 and RS6) which are non-neurovirulent when injected into adult mouse brains. 2) A strain of HSV-I (KOS) which is nonvirulent in mice when injected in foot pads. 3) A revertant of a ts mutant of HSV-I (tsI) which is not temperature sensitive for replication in non-nervous tissues, but which does not reactivate from the latent state in spinal ganglia at 38.5?0?C. In addition, the inability of HSV-I to invade mesoderm in the CAM of embryonic chicks is being investigated. In all cases, trivial explanations for the altered pathogenicity have been rigorously excluded. Data are presented demonstrating that pathogenesis can be rescued using DNA transfections of wild-type parental DNA restriction fragments (molecularly cloned) and intact variant virus DNA followed by selection in vivo. A combined collaborative study of the genes and gene products involved in these and related examples of HSV pathology and neurovirulence using techniques of both molecular biology and pathobiology is described.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI006246-21
Application #
3124274
Study Section
Experimental Virology Study Section (EVR)
Project Start
1978-11-01
Project End
1990-06-30
Budget Start
1985-09-01
Budget End
1986-06-30
Support Year
21
Fiscal Year
1985
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

O'Neil, J E; Loutsch, J M; Aguilar, J S et al. (2004) Wide variations in herpes simplex virus type 1 inoculum dose and latency-associated transcript expression phenotype do not alter the establishment of latency in the rabbit eye model. J Virol 78:5038-44
Marquart, M E; Zheng, X; Tran, R K et al. (2001) A cAMP response element within the latency-associated transcript promoter of HSV-1 facilitates induced ocular reactivation in a mouse hyperthermia model. Virology 284:62-9
Bloom, D C; Stevens, J G (1994) Neuron-specific restriction of a herpes simplex virus recombinant maps to the UL5 gene. J Virol 68:3761-72
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
Yuhasz, S A; Dissette, V B; Cook, M L et al. (1994) Murine cytomegalovirus is present in both chronic active and latent states in persistently infected mice. Virology 202:272-80
Huang, C J; Rice, M K; Devi-Rao, G B et al. (1994) The activity of the pseudorabies virus latency-associated transcript promoter is dependent on its genomic location in herpes simplex virus recombinants as well as on the type of cell infected. J Virol 68:1972-6
Huang, C J; Goodart, S A; Rice, M K et al. (1993) Mutational analysis of sequences downstream of the TATA box of the herpes simplex virus type 1 major capsid protein (VP5/UL19) promoter. J Virol 67:5109-16
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
Guzowski, J F; Wagner, E K (1993) Mutational analysis of the herpes simplex virus type 1 strict late UL38 promoter/leader reveals two regions critical in transcriptional regulation. J Virol 67:5098-108
Sedarati, F; Margolis, T P; Stevens, J G (1993) Latent infection can be established with drastically restricted transcription and replication of the HSV-1 genome. Virology 192:687-91

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