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Journal of Virology, April 2001, p. 3121-3128, Vol. 75, No. 7
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.7.3121-3128.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Computational Analysis of Retrovirus-Induced scid Cell Death

René Daniel, Samuel Litwin, Richard A. Katz, and Anna Marie Skalka*

Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111

Received 7 July 2000/Accepted 11 January 2001

It was shown recently that retroviral infection induces integrase-dependent apoptosis (programmed cell death) in DNA-dependent protein kinase (DNA-PK)-deficient scid pre-B cell lines, and it has been proposed that retroviral DNA integration is perceived as DNA damage that is repairable by the DNA-PK-dependent nonhomologous end-joining pathway (R. Daniel, R. A. Katz, and A. M. Skalka, Science 284:644-647, 1999). Very few infectious virions seem to be necessary to induce scid cell death. In this study, we used a modeling approach to estimate the number of integration events necessary to induce cell death of DNA-PK-deficient scid cells. Several models for integration-mediated cell killing were considered. Our analyses indicate that a single hit (integration event) is sufficient to kill a scid cell. Moreover, the closest fit between the experimental data and our computational simulations was achieved with a model in which the infected scid cell must pass through S phase to trigger apoptosis. This model is consistent with the findings that a single double-strand DNA break is sufficient to kill a cell deficient in DNA repair and illustrates the potential of a modeling approach to address quantitative aspects of virus-cell interactions.

* Corresponding author. Mailing address: Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Ave., Philadelphia, PA 19111. Phone: (215) 728-2490. Fax: (215) 728-2778. E-mail: AM_Skalka{at}fccc.edu.

Journal of Virology, April 2001, p. 3121-3128, Vol. 75, No. 7
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.7.3121-3128.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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