The eight human herpes viruses share the ability to initiate a primary infection in a specific target tissue and to subsequently sequester themselves in a latent form. The viruses that compose this family are grouped into three classes on the basis of the site of where their primary infection occurs and where they are found during latency. Two members of this family Epstein Barr and Kaposi's Sarcoma have been implicated in the generation of tumors in humans. Regulation of gene expression from these large double-stranded DNA containing viruses results from a temporally ordered cascade of gene expression. This grant is concerned with regulation of gene expression in cells infected with herpes simplex virus (HSV), the prototype for the alphaherpesviridae. It is the expression of immediate early (IE) genes that is responsible for coordinate regulation of HSV gene expression. This laboratory has focused its efforts on characterizing the activities of IE gene products. In particular we have studied the gene products of the IE-O, IE-4 and IE-27 loci. These analyses have revealed novel functions for both ICPO and ICP27, and demonstrated that ICPs 4 and 27 interact. The novel feature of ICP27 that will be studied in this application is its RNA- dependent shuttling activity. We will continue our studies of these gene products using genetic and biochemical approaches to examine the effects of mutations to the sequences encoding these proteins. These studies will add to the understanding of how these viruses interact with their host and what the consequences of virus specified protein-protein and host-virus interactions are.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI033952-06
Application #
2758865
Study Section
Virology Study Section (VR)
Program Officer
Beisel, Christopher E
Project Start
1993-12-01
Project End
2003-11-30
Budget Start
1998-12-01
Budget End
1999-11-30
Support Year
6
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
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Panagiotidis, C A; Silverstein, S J (1999) The host-cell architectural protein HMG I(Y) modulates binding of herpes simplex virus type 1 ICP4 to its cognate promoter. Virology 256:64-74
Lium, E K; Panagiotidis, C A; Wen, X et al. (1998) The NH2 terminus of the herpes simplex virus type 1 regulatory protein ICP0 contains a promoter-specific transcription activation domain. J Virol 72:7785-95
Soliman, T M; Sandri-Goldin, R M; Silverstein, S J (1997) Shuttling of the herpes simplex virus type 1 regulatory protein ICP27 between the nucleus and cytoplasm mediates the expression of late proteins. J Virol 71:9188-97

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