Differential cell killing by lymphomagenic murine leukemia viruses occurs independently of p53 activation and mitochondrial damage.
Upon inoculation into AKR mice, mink cell focus-forming murine leukemia virus (MCF MLV) accelerates thymic lymphoma formation. During the preleukemic phase of disease, we observed the induction of apoptosis in thymic lymphocytes. A similar induction of apoptosis was observed for cultured mink epithelial cells after MCF13 MLV infection. In this study, the relevance of viral pathogenicity to cell killing was determined by testing the susceptibility of various cell types from different species to lymphomagenic MLVs. We observed that the cytopathic effect of lymphomagenic MLVs was restricted to mink cells. Southern blot analysis of MLV-infected cells revealed an accumulation of the linear form of unintegrated viral DNA, particularly in mink cells after MCF13 MLV infection. Thus, a strong correlation was observed between viral superinfection, which results in the accumulation of high levels of unintegrated viral DNA, and cell killing. Immunoblot analysis for MCF13 MLV-infected mink epithelial cells did not show a significant change in total p53 levels or its phosphorylated form at Ser-15 compared with that in mock-treated cells. Moreover, a time course analysis for mink epithelial cells infected with MCF13 MLV did not reveal mitochondrial depolarization or a significant change in Bax levels. These results demonstrate that MCF13 MLV induces apoptosis preferentially in cells in which superinfection occurs, and the mechanism involved is independent of p53 activation and mitochondrial damage.
Nanua
Suparna
S
Department of Immunology and Microbiology and the Karmanos Cancer Institute, Wayne State University, 540 E. Canfield Avenue, Detroit, MI 48201, USA..
Yoshimura
Fayth K
FK
D000818:Animals; D017209:Apoptosis; D004249:DNA Damage; D051379:Mice; D008907:Mink; D008908:Mink Cell Focus-Inducing Viruses / Q000472:pathogenicity*; D008928:Mitochondria / Q000502:physiology*; D041681:NIH 3T3 Cells; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D016159:Tumor Suppressor Protein p53