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Adenovirus genes that modulate the sensitivity of virus-infected cells to lysis by TNF

✍ Scribed by William S. M. Wold

Publisher
John Wiley and Sons
Year
1993
Tongue
English
Weight
664 KB
Volume
53
Category
Article
ISSN
0730-2312

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✦ Synopsis

TNF is a key inflammatory cytokine with antiviral properties. Human adenoviruses encode several intracellular proteins that mediate the effects of TNF. Expression of the adenovirus immediate early EIA proteins induces viral genes and a host of cellular genes, drives Go cells into S-phase, and induces apoptosis and susceptibility to TNF-induced apoptosis. The adenovirus E l B-I 9K protein inhibits both EIA-and TNF-induced apoptosis. The E3-14.7K protein and the E3-10.4K/I 4.5K complex of proteins inhibit TNF-but not E l A-induced apoptosis. The E3 14.7K and 10.4K/14.5K proteins inhibit TNF activation of cytosolic phospholipase A2 (cPLA,), which may explain how they inhibit TNF cytolysis. Since eicosinoids produced from arachidonic acid (the product of cPLA,) are potent mediators of inflammation, the E3 proteins may block the inflammatory response to adenovirus infection. These adenovirus proteins should be novel tools to understand adenovirus pathogenesis, TNF signal transduction, and TNF

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