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This was achieved by replacement of the viral TAR-Tat system for transcriptional activation by the Escherichia coli-derived Tet system for inducible gene expression. This HIV-rtTA virus replicates in a strictly dox-dependent manner. In this virus, additional deletions and\/or inactivating mutations were introduced in the genes for accessory proteins. These proteins are essential for virus replication in untransformed cells, but dispensable in leukemic T cells. These minimized HIV-rtTA variants contain up to 7 deletions\/inactivating mutations (TAR, Tat, vif, vpR, vpU, nef and U3) and replicate efficiently in the leukemic SupT1 T cell line, but do not replicate in normal peripheral blood mononuclear cells. These virus variants are also able to efficiently remove leukemic cells from a mixed culture with untransformed cells. The therapeutic viruses use CD4 and CXCR4 for cell entry and could potentially be used against CXCR4 expressing malignancies such as T-lymphoblastic leukemia\/lymphoma, NK leukemia and some myeloid leukemias.<\/jats:p>","DOI":"10.1186\/1742-4690-3-64","type":"journal-article","created":{"date-parts":[[2006,9,27]],"date-time":"2006-09-27T18:24:59Z","timestamp":1159381499000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Construction of doxycyline-dependent mini-HIV-1 variants for the development of a virotherapy against leukemias"],"prefix":"10.1186","volume":"3","author":[{"given":"Rienk E","family":"Jeeninga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Jan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk","family":"van den Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Berkhout","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2006,9,27]]},"reference":[{"key":"506_CR1","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1099\/0022-1317-83-3-491","volume":"83","author":"CJ Ring","year":"2002","unstructured":"Ring CJ: Cytolytic viruses as potential anti-cancer agents. 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