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Journal of Virology, August 2006, p. 7807-7815, Vol. 80, No. 16
0022-538X/06/$08.00+0     doi:10.1128/JVI.00198-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Effects of Adeno-Associated Virus on Adenovirus Replication and Gene Expression during Coinfection

Jennifer M. Timpe, Kristin C. Verrill, and James P. Trempe*

Department of Biochemistry and Cancer Biology, Medical University of Ohio, 3035 Arlington Ave., Toledo, Ohio 43614-5804

Received 27 January 2006/ Accepted 31 May 2006

Adeno-associated virus (AAV) is a nonpathogenic parvovirus that requires adenovirus (Ad) or another helper virus for a fully permissive infection. AAV-mediated inhibition of Ad is well documented, yet many details of this interaction remain unclear. In this study, we observed a maximum 50-fold decrease in infectious virus production and a 10- to 40-fold reduction in Ad DNA synthesis during coinfections with AAV. With the exception of the E3 gene, AAV decreased all steady-state Ad mRNA levels at 24 h postinfection (hpi) in a dose-dependent manner. However, not all transcription units were affected equally. E4 and late transcription were the most strongly inhibited, and E1A and E2A were the least affected. The temporal effects of AAV on Ad mRNA transcript levels also varied among the Ad genes. Ad protein expression paralleled mRNA levels at 24 hpi, suggesting that coinfecting AAV does not exert substantial effects on translation. In plasmid transfection assays, Rep78 protein most effectively limited Ad amplification, while Rep40 had no effect. Since E2a and E4 proteins are essential for efficient Ad DNA amplification, we examined the relationship between reduced E2A and E4 expression and decreased DNA amplification. Transfected Rep78 did not reduce E2A and E4 transcript levels prior to DNA replication. Also, AAV-induced inhibition of E2A and E4 mRNA production did not occur in the presence of hydroxyurea. It is therefore unlikely that decreased early gene expression is solely responsible for AAV's suppression of Ad DNA replication. Our results suggest that AAV amplification and/or Rep gene expression inhibits Ad DNA synthesis.

* Corresponding author. Mailing address: Department of Biochemistry and Cancer Biology, Medical University of Ohio, 3035 Arlington Ave., Toledo, OH 43614-5804. Phone: (419) 383-4103. Fax: (419) 383-6228. E-mail: jtrempe{at}meduohio.edu.

Journal of Virology, August 2006, p. 7807-7815, Vol. 80, No. 16
0022-538X/06/$08.00+0     doi:10.1128/JVI.00198-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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