The major goals of the research proposed in this application are to gain understanding of the functions of the viral gene products required for and controlling viral transformation and replication.
The specific aims to be pursued are: 1) to characterize recently isolated mutants with deletions in either E1A or E1B in order to investigate the gene products required for cell transformation and regulatory interactions between viral transcription units; 2) to develop a general method of gene-directed mutagenesis in order to select from each of the early transcription regions a number of conditionally lethal, temperature-sensitive (ts) mutants to permit functional studies of the gene products regulating replication and transformation; and 3) to investigate the early viral and cellular DNA interactions leading to transformation using a) newly developed rat cell line which transforms at a relatively high frequency, and b) selected mutants which transform at either high or low frequency.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI012052-12
Application #
3125090
Study Section
Virology Study Section (VR)
Project Start
1977-09-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
12
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Ginsberg, H S; Moldawer, L L; Prince, G A (1999) Role of the type 5 adenovirus gene encoding the early region 1B 55-kDa protein in pulmonary pathogenesis. Proc Natl Acad Sci U S A 96:10409-11
Tang, Q; Lundholm-Beauchamp, U; Ginsberg, H S (1997) Spontaneous occurrence of early region 1A reiteration mutants of type 5 adenovirus in persistently infected human T-lymphocytes. Virology 230:281-91
Ginsberg, H S (1996) The ups and downs of adenovirus vectors. Bull N Y Acad Med 73:53-8
Tang, Q; Ginsberg, H S (1994) trans-dominant interference of type 5 adenovirus E1a mutants in cell transformation. J Virol 68:2127-34
Weiden, M D; Ginsberg, H S (1994) Deletion of the E4 region of the genome produces adenovirus DNA concatemers. Proc Natl Acad Sci U S A 91:153-7
Ginsberg, H S; Prince, G A (1994) The molecular basis of adenovirus pathogenesis. Infect Agents Dis 3:1-8
Hotta, J; Shi, L; Ginsberg, H S (1994) Effect of CD4 gene expression on adenovirus replication. J Virol 68:7284-91
Ginsberg, H S; Moldawer, L L; Sehgal, P B et al. (1991) A mouse model for investigating the molecular pathogenesis of adenovirus pneumonia. Proc Natl Acad Sci U S A 88:1651-5
Ginsberg, H S; Horswood, R L; Chanock, R M et al. (1990) Role of early genes in pathogenesis of adenovirus pneumonia. Proc Natl Acad Sci U S A 87:6191-5
Ginsberg, H S; Lundholm-Beauchamp, U; Horswood, R L et al. (1989) Role of early region 3 (E3) in pathogenesis of adenovirus disease. Proc Natl Acad Sci U S A 86:3823-7

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