Measles virus (MV) is a negative strand RNA virus of the family Paramyxoviridae, and the attenuated Edmonston-B strain can be engineered by the reverse genetics system. Here we constructed the recombinant Edmonston st...Measles virus (MV) is a negative strand RNA virus of the family Paramyxoviridae, and the attenuated Edmonston-B strain can be engineered by the reverse genetics system. Here we constructed the recombinant Edmonston strain of measles virus (MV-Ed) that expressed hepatitis C virus (HCV) envelope proteins (rMV-E1E2). The rMV-E1E2 successfully expressed HCV E1 and E2 proteins. To evaluate its immunogenicity, NOD/Scid/Jak3null mice that were engrafted with human peripheral blood mononuclear cells (huPBMC-NOJ) were infected with this rMV-E1E2. Although human lymphocytes could be isolated from the spleens of mock-infected mice during the 2-weeks-long experiment, the proportion of mice that were infected with MV or rMV-E1E2 was decreased in a viral dose-dependent manner. Over 103 PFU of virus infection decreased the human PBL to less than 5%. Significant decrease of B cell population in human PBL from rMV-E1E2 infected NOD-SCID mice and decrease of T cell population in those from MV infected mice were observed. Human antibody production in these mice was also examined. Thus, the results in this study may contribute for future improvement of recombinant vaccine using measles virus vector.展开更多
Patients with Philadelphia chromosome (p190 BCR-ABL fusion gene)-positive acute lymphoblastic leukemia have a poor prognosis despite intensive therapeutic intervention.In this study, we attempted to develop a leukemia...Patients with Philadelphia chromosome (p190 BCR-ABL fusion gene)-positive acute lymphoblastic leukemia have a poor prognosis despite intensive therapeutic intervention.In this study, we attempted to develop a leukemia nonhuman primate model that mimics various human systems. Hematopoietic stem/progenitor cells in the common marmoset were transduced with a lentiviral vector containing the p190 BCR-ABL fusion gene by ex vivo transduction or in vivo direct bone marrow injection. In the latter model, BCR-ABL gene expression was maintained for more than one and a half years. One marmoset unexpectedly developed myelofibrosis-like disease. However, none of the marmosets have developed leukemia to date. In conclusion, we successfully achieved sustained p190 BCR-ABL gene expression in vivo. However, a genetic mutation in addition to p190 BCR-ABL may be required for the malignant transformation of hematopoietic stem/progenitor cells in the common marmoset during the short observation period. This novel in vivo approach will help develop a marmoset leukemia model in the future.展开更多
文摘Measles virus (MV) is a negative strand RNA virus of the family Paramyxoviridae, and the attenuated Edmonston-B strain can be engineered by the reverse genetics system. Here we constructed the recombinant Edmonston strain of measles virus (MV-Ed) that expressed hepatitis C virus (HCV) envelope proteins (rMV-E1E2). The rMV-E1E2 successfully expressed HCV E1 and E2 proteins. To evaluate its immunogenicity, NOD/Scid/Jak3null mice that were engrafted with human peripheral blood mononuclear cells (huPBMC-NOJ) were infected with this rMV-E1E2. Although human lymphocytes could be isolated from the spleens of mock-infected mice during the 2-weeks-long experiment, the proportion of mice that were infected with MV or rMV-E1E2 was decreased in a viral dose-dependent manner. Over 103 PFU of virus infection decreased the human PBL to less than 5%. Significant decrease of B cell population in human PBL from rMV-E1E2 infected NOD-SCID mice and decrease of T cell population in those from MV infected mice were observed. Human antibody production in these mice was also examined. Thus, the results in this study may contribute for future improvement of recombinant vaccine using measles virus vector.
文摘Patients with Philadelphia chromosome (p190 BCR-ABL fusion gene)-positive acute lymphoblastic leukemia have a poor prognosis despite intensive therapeutic intervention.In this study, we attempted to develop a leukemia nonhuman primate model that mimics various human systems. Hematopoietic stem/progenitor cells in the common marmoset were transduced with a lentiviral vector containing the p190 BCR-ABL fusion gene by ex vivo transduction or in vivo direct bone marrow injection. In the latter model, BCR-ABL gene expression was maintained for more than one and a half years. One marmoset unexpectedly developed myelofibrosis-like disease. However, none of the marmosets have developed leukemia to date. In conclusion, we successfully achieved sustained p190 BCR-ABL gene expression in vivo. However, a genetic mutation in addition to p190 BCR-ABL may be required for the malignant transformation of hematopoietic stem/progenitor cells in the common marmoset during the short observation period. This novel in vivo approach will help develop a marmoset leukemia model in the future.
