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Journal of Virology, September 2002, p. 8910-8919, Vol. 76, No. 17
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.17.8910-8919.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Transgenic Expression in Mouse Lung Reveals Distinct Biological Roles for the Adenovirus Type 5 E1A 243- and 289-Amino-Acid Proteins

Yongping Yang,^1* Colin McKerlie,^2,3 Steven H. Borenstein,⁴ Zhan Lu,¹ Marco Schito,⁴ John W. Chamberlain,^4,5 and Manuel Buchwald^1,6

Programs in Genetics and Genomic Biology,¹ Immunity, Infection, Injury and Repair, Research Institute, Hospital for Sick Children,⁴ Departments of Molecular and Medical Genetics,⁶ Immunology,⁵ Laboratory Medicine and Pathobiology, University of Toronto,² Molecular and Cellular Biology Research Program, Sunnybrook & Women's College Health Science Centre, Toronto, Ontario, Canada³

Received 22 March 2002/ Accepted 6 June 2002

Little is known about the biological significance of human adenovirus type 5 (Ad5) E1A in vivo. However, Ad5 E1A is well defined in vitro and can be detected frequently in the lungs of patients with pulmonary disease. Transgenic expression of the Ad5 E1A gene targeted to the mouse lung reveals distinct biological effects caused by two Ad5 E1A products. Either of two Ad5 E1A proteins was preferentially expressed in vivo in the transgenic lungs. The preferential expression of the Ad5 E1A 243-amino-acid (aa) protein at a moderate level was associated with cellular hyperplasia, nodular lesions of proliferating lymphocyte-like cells, and a low level of p53-dependent apoptosis in the lungs of transgenic mice. In contrast, the preferential expression of the Ad5 E1A 289-aa protein at a moderate level resulted in a proapoptotic injury and an acute pulmonary proinflammation in the lungs of transgenic mice, mediated by multiple apoptotic pathways, as well as an enhancement of the host immune cell response. Expression of the Ad5 E1A 243-aa protein resulted in proliferation-stimulated p53 upregulation, while expression of the Ad5 E1A 289-aa protein led to DNA damage-induced p53 activation. These data suggest that the Ad5 E1A 243- and 289-aa proteins lead to distinct biological roles in vivo.

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* Corresponding author. Present address: Genetics of Cancer Susceptibility, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute at Frederick, Bldg. 560, Room 32-16, P.O. Box B, Frederick, MD 21702. Phone: (301) 846-5137. Fax: (301) 846-6323. E-mail: yongpiny{at}mail.nih.gov.

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Journal of Virology, September 2002, p. 8910-8919, Vol. 76, No. 17
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.17.8910-8919.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

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• Behzad, A. R., Morimoto, K., Gosselink, J., Green, J., Hogg, J. C., Hayashi, S. (2006). Induction of mesenchymal cell phenotypes in lung epithelial cells by adenovirus E1A. Eur Respir J 28: 1106-1117 [Abstract] [Full Text]