Abstract

The broad goals of the research proposed in this application are directed toward gaining knowledge of the molecular reactions essential in several of adenovirus' pathogenic processes: acute pneumonia, latent or persistent infections, and cellular transformation. To approach these goals the following specific aims will be pursued: 1) Identification of the gene functions essential for pathogenesis of pneumonia in an animal model that pathologically is similar to that in humans, i.e., infection of the cotton rat; 2) Study of the mechanisms of the establishment of persistent infections of human T-4 lymphocytes; and 3) Investigate the mechanism by which the early regions 1a and 1b induce and maintain cellular transformation. One other specific aim will also be followed: Complete the characterization of newly isolated conditionally lethal, temperature-sensitive mutants of the E2a DNA-binding protein to attain better understanding of the several functions of this protein.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI012052-17
Application #
3125094
Study Section
Virology Study Section (VR)
Project Start
1977-09-01
Project End
1992-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
17
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027

  Publications

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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