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

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.

journal_name

J Virol

journal_title

Journal of virology

authors

Yang Y,McKerlie C,Borenstein SH,Lu Z,Schito M,Chamberlain JW,Buchwald M

doi

10.1128/jvi.76.17.8910-8919.2002

subject

Has Abstract

pub_date

2002-09-01 00:00:00

pages

8910-9

issue

17

eissn

0022-538X

issn

1098-5514

journal_volume

76

pub_type

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