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Journal of Virology, October 2009, p. 10286-10292, Vol. 83, No. 19
0022-538X/09/$08.00+0     doi:10.1128/JVI.00343-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Adeno-Associated Virus Type 2 Induces Apoptosis in Human Papillomavirus-Infected Cell Lines but Not in Normal Keratinocytes {triangledown}

Samina Alam and Craig Meyers*

Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033

Received 16 February 2009/ Accepted 13 July 2009

The results of seroepidemiological studies suggest that infection with adeno-associated virus type 2 (AAV2) is negatively correlated with the incidence of human papillomavirus (HPV)-associated cervical cancer. We studied the potential of AAV2 oncosuppression of HPV and showed that HPV/AAV2 coinfection of cells culminated in apoptotic death, as determined by DNA laddering and caspase-3 cleavage. The induction of apoptosis coincided with AAV2 Rep protein expression; increased S-phase progression; upregulated pRb displaying both hyper- and hypophosphorylated forms; increased levels of p21WAF1, p16INK4, and p27KIP1 proteins; and diminished levels of E7 oncoprotein. In contrast, normal keratinocytes that were infected with AAV2 or transfected with the cloned full-length AAV2 genome failed to express Rep proteins or undergo apoptosis. The failure of AAV2 to productively infect normal keratinocytes could be clinically advantageous. The delineation of the molecular mechanisms underlying the HPV/AAV2 interaction could be harnessed for developing novel AAV2-derived therapeutics for cervical cancer.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033. Phone: (717) 531-6240. Fax: (717) 531-4600. E-mail: cmm10{at}psu.edu

{triangledown} Published ahead of print on 22 July 2009.

Journal of Virology, October 2009, p. 10286-10292, Vol. 83, No. 19
0022-538X/09/$08.00+0     doi:10.1128/JVI.00343-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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