Abstract

Acute adenoviral infection has been associated with severe lung disease. Chronic sequelae may also result from adenoviral infection, such as hyperlucent lung syndrome and chronic obstructive lung disease. Various cytokines, especially tumor necrosis factor (TNF) appear to be necessary for the development of many acute and chronic lung diseases. Since the early genes of adenovirus are expressed during latency and during acute infection, the regulation of cytokine production by -these genes may be important in the pathogenesis of both acute and chronic sequelae of adenoviral infection. The purpose of this proposal is to advance our understanding of the mechanisms by which adenovirus regulates the TNF gene. We will first assess whether adenovirus early genes can upregulate the TNF gene. Next, we will examine the mechanism of this regulation both from the standpoint of the viral genome and from the standpoint of the TNF gene itself. Finally, we will assess whether or not these same mechanisms are important in the regulation of TNF by whole adenovirus following acute infection of human inflammatory cell lines in vitro.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL003106-04
Application #
2027029
Study Section
Special Emphasis Panel (ZHL1-CCT-L (F1))
Project Start
1994-09-30
Project End
1999-12-31
Budget Start
1997-01-01
Budget End
1997-12-31
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of Oklahoma Health Sciences Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73117

  Publications

Sanchez, Traci A; Booth, J Leland; Metcalf, Jordan P (2002) Tumor necrosis factor-alpha activation by adenovirus E1A 13S CR3 occurs in a cell-dependent and cell-independent manner. Am J Physiol Lung Cell Mol Physiol 283:L619-27
Alcorn, M J; Booth, J L; Coggeshall, K M et al. (2001) Adenovirus type 7 induces interleukin-8 production via activation of extracellular regulated kinase 1/2. J Virol 75:6450-9
Sanchez, T A; Habib, I; Leland Booth, J et al. (2000) Zinc finger and carboxyl regions of adenovirus E1A 13S CR3 are important for transactivation of the cytomegalovirus major immediate early promoter by adenovirus. Am J Respir Cell Mol Biol 23:670-7
Hitt, D C; Booth, J L; Dandapani, V et al. (2000) A flow cytometric protocol for titering recombinant adenoviral vectors containing the green fluorescent protein. Mol Biotechnol 14:197-203
Leland Booth, J; Metcalf, J P (1999) Type-specific induction of interleukin-8 by adenovirus. Am J Respir Cell Mol Biol 21:521-7