The overall goal of this proposal is to understand further the functions of HSV-1 Alpha-polypeptide, ICP-4, during cytolytic infection. HSV ICP-4 regulates positively the appearance of HSV Beta-polypeptides which are necessary for viral replication during productive infection. The focus of this proposal is to ascertain whether ICP-4 may act as a determinant HSV pathogenesis by modulating the expression of specific cellular genes. Cellular genes whose expression is regulated by HSV ICP-4 activity during cytolytic infection will be defined, isolated, and characterized by molecular hybridization and cDNA cloning techniques. Determination of the specificity with which ICP-4 exerts regulation on cell gene expression will be achieved by assaying cell transcripts of candidate cell cDNA clones following infection of cells with a panel of ts mutants for ICP-4. Identification of isolated cDNA clones will afforded by DNA sequence analysis followed by comparison with DNA sequences for known eukaryotic genes provided in the Los Alamos Databank. Trans and/or cis mechanisms of ICP-4 regulation of candidate cellular genes will be evaluated by transient expression assays following transfection of mammalian expression vectors containing combinations of ICP-4, HSV TK, and various portions of candidate genomic cell genes into appropriate host cells. Results from these successive series of experiments will define more definitively the multifunctional roles of HSV-1 ICP-4 in viral pathogenesis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R23)
Project #
5R23CA036143-03
Application #
3446504
Study Section
Virology Study Section (VR)
Project Start
1984-07-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Type
Overall Medical
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390