Transgenic expression in mouse lung reveals distinct biological roles for the adenovirus type 5 E1A 243- and 289-amino-acid proteins

Yongping Yang, Colin McKerlie, Steven H. Borenstein, Zhan Lu, Marco Schito, John W. Chamberlain, Manuel Buchwald

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)8910-8919
Number of pages10
JournalJournal of Virology
Volume76
Issue number17
DOIs
StatePublished - 2002
Externally publishedYes

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Adenoviridae
lungs
Amino Acids
gene expression
Lung
amino acids
mice
Proteins
proteins
Transgenic Mice
genetically modified organisms
Adenovirus E1A Proteins
Human Adenoviruses
Lung Injury
Lung Diseases
DNA Damage
Hyperplasia
Up-Regulation
hyperplasia
lesions (animal)

ASJC Scopus subject areas

  • Immunology

Cite this

Transgenic expression in mouse lung reveals distinct biological roles for the adenovirus type 5 E1A 243- and 289-amino-acid proteins. / Yang, Yongping; McKerlie, Colin; Borenstein, Steven H.; Lu, Zhan; Schito, Marco; Chamberlain, John W.; Buchwald, Manuel.

In: Journal of Virology, Vol. 76, No. 17, 2002, p. 8910-8919.

Research output: Contribution to journalArticle

Yang, Yongping ; McKerlie, Colin ; Borenstein, Steven H. ; Lu, Zhan ; Schito, Marco ; Chamberlain, John W. ; Buchwald, Manuel. / Transgenic expression in mouse lung reveals distinct biological roles for the adenovirus type 5 E1A 243- and 289-amino-acid proteins. In: Journal of Virology. 2002 ; Vol. 76, No. 17. pp. 8910-8919.
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