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37. Protection of Retrovirus-induced Disease by Transplantation of Bone Marrow Cells Transduced with MuLV Env Gene via Retrovirus Vector
Shiro Aizawa, Hitoko Kamisaku and Masanobu Kitagawa*
(*Tokyo Medical and Dental Univ.)
Keywords: gene therapy, bone marrow transplantation, Fv-4, virus resistance, retrovirus vector
Fv-4 is a mouse gene that dominantly confers resistance to infection by ecotropic murine leukemia virus (MuLV). We have demonstrated previously that bone marrow chimeras in which hematopoietic cells were replaced with cells expressing Fv-4 resistant (Fv-4r) gene product became refractory to Friend leukemia virus (FLV)-induced leukemogenesis. To induce in vivo resistance against retrovirus-induced diseases by retroviral vector-mediated gene transducton, we introduced Fv-4r env gene into bone marrow cells of FLV-susceptible C3H/He (C3H) mice with retroviral vector (pLSF) derived from murine Friend spleen focus forming virus (SFFV) and the cells were transplanted into lethally irradiated C3H mice. After the bone marrow transplantation, Fv-4r gene product was succesfully expressed on erythroid and myeloid cells, while lymphoid cells were only weakly expressing Fv-4r gene product. The C3H mice expressing relatively higher amounts of Fv-4r gene product were rendered resistant to FLV-induced erythroleukemia, while mice expressing lower amounts of the Fv-4r gene product were still susceptible. Effective protection of FLV-induced leukemia in these mice suggested that the Fv-4r gene expression by erythroid cells which were the major target for FLV infection might be critical for resisting FLV-induced leukemia. Thus, a gene therapy model by transducing Fv-4r env gene using bone marrow transplantation would provide a useful protection model system of retrovirus-induced diseases.
Publications:
Kitagawa, M., Aizawa, S., Kamisaku, M., Hirokawa, K. and Ikeda, H.: Exp. Hematol. 27, 234-241, 1999.
