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Journal of Virology, July 2001, p. 6007-6015, Vol. 75, No. 13
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.13.6007-6015.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Mink Cell Focus-Forming Murine Leukemia Virus Killing of Mink Cells Involves Apoptosis and Superinfection

Fayth K. Yoshimura,1,2,* Tao Wang,1 and Suparna Nanua1

Department of Immunology and Microbiology1 and the Karmanos Cancer Institute,2 Wayne State University, Detroit, Michigan 48201

Received 8 February 2001/Accepted 12 April 2001

Induction of apoptosis by different types of pathogenic retroviruses is an important step in disease development. We have observed that infection of thymic lymphocytes by the mink cell focus-forming murine leukemia virus (MCF MLV) during the preleukemic period resulted in an enhancement of apoptosis of these cells. To further study the ability of MCF MLVs to induce apoptosis and the role of this process in viral pathogenesis, we have developed an in vitro system of virus-induced apoptosis. MCF13 MLV infection of mink epithelial cells resulted in the production of cytopathic foci. In contrast, infection of mink cells with the 4070A amphotropic MLV did not produce any cytopathic effects. Staining of MCF13 MLV-infected cells with propidium iodide and annexin V-fluorescein isothiocyanate indicated that virus-induced cell death was due to apoptosis. At 6 days postinfection, the percentage of apoptotic MCF13 MLV-infected cells was 27% compared with 2 to 3% for mock- or amphotropic MLV-infected cells, representing a 9- to 14-fold difference. Assays for caspase-3 activation confirmed the detection by flow cytometry of apoptosis of MCF13 MLV-infected cells. Large amounts of unintegrated linear viral DNA were detectable by Southern blot analysis during the acute phase of infection, which indicated that MCF13 MLV is able to superinfect mink cells. Unintegrated viral DNA of only the linear form was detectable in thymic lymphocytes isolated from MCF13 MLV-inoculated mice during the preleukemic period. These results indicated that the ability of MCF13 MLV to induce apoptosis is correlated with its ability to superinfect cells and that this occurs as an early step in thymic lymphoma development.

* Corresponding author. Mailing address: Department of Immunology and Microbiology, Wayne State University, 540 E. Canfield Ave., Detroit, MI 48201. Phone: (313) 577-1571. Fax: (313) 577-1155. E-mail: fyoshi{at}med.wayne.edu.

Journal of Virology, July 2001, p. 6007-6015, Vol. 75, No. 13
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.13.6007-6015.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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