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Journal of Virology, July 2003, p. 7936-7944, Vol. 77, No. 14
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.14.7936-7944.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Mutual Interference of Adenovirus Infection and myc Expression{dagger}

Kristina Löhr,1 Oliver Hartmann,2 Helmut Schäfer,2 and Matthias Dobbelstein1*

Institut für Virologie,1 Institut für Medizinische Biometrie und Epidemiologie, Philipps-Universität Marburg, 35037 Marburg, Germany2

Received 26 February 2003/ Accepted 24 April 2003

During infection with adenovirus, massive changes in the transcription of virus genes are observed, suggesting that the expression of cellular genes may also be modulated. To characterize the levels of cellular RNA species in infected cells, cDNA arrays were screened 24 h after infection of HeLa cells with wild-type adenovirus type 5, strain dl309. Despite complete transduction of the cells, fewer than 20 cellular genes (out of 4,600 analyzed and 1,200 found detectable and expressed above background) were altered more than threefold in their corresponding RNA levels compared to mock-infected cells. In particular, the expression of the myc oncogene was reduced at the mRNA level. This reduction was dependent on the replication of virus DNA and partially dependent on the presence of the adenovirus gene products E1B-55 kDa and E4orf6, but not E4orf3. On the other hand, MYC protein had an increased half-life in infected cells, resulting in roughly constant steady-state protein levels. The adenovirus E1A gene product is necessary and sufficient to stabilize MYC. Overexpressed MYC inhibited adenovirus replication and the proper formation of the virus replication centers. We conclude that adenovirus infection leads to the stabilization of MYC, perhaps as a side effect of E1A activities. On the other hand, myc mRNA levels are negatively regulated during adenovirus infection, and this may avoid the detrimental effect of excessive MYC on adenovirus replication.

* Corresponding author. Mailing address: Institut für Virologie, Philipps-Universität Marburg, Robert Koch Strasse 17, 35037 Marburg, Germany. Phone: 49 6421 28 64318. Fax: 49 6421 28 68962. E-mail: dobbelst{at}mailer.uni-marburg.de.

{dagger} We dedicate this paper to Hans-Dieter Klenk on the occasion of his 65th birthday in appreciation of his generous and continuous support.

Journal of Virology, July 2003, p. 7936-7944, Vol. 77, No. 14
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.14.7936-7944.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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