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  • Title: Modulation of Moloney leukemia virus long terminal repeat transcriptional activity by the murine CD4 silencer in retroviral vectors.
    Author: Indraccolo S, Minuzzo S, Habeler W, Zamarchi R, Fregonese A, Günzburg WH, Salmons B, Uckert W, Chieco-Bianchi L, Amadori A.
    Journal: Virology; 2000 Oct 10; 276(1):83-92. PubMed ID: 11021997.
    Abstract:
    We investigated whether CD4 gene regulatory sequences might be useful for developing transcriptionally targeted Moloney murine leukemia virus (Mo-MLV)-based retroviral vectors for gene expression specifically in CD4(+) cells. We could modulate Mo-MLV long terminal repeat (LTR) activity by inserting a 438-bp-long fragment containing the murine CD4 silencer in the LTR of the vector; both beta-galactosidase and green fluorescent protein reporter gene activities were strongly down-regulated in both murine and human CD8(+) cells, but not in CD4(+) lymphoid cell lines and freshly isolated lymphocytes transduced with this vector, compared with the findings using a control vector carrying wild-type LTRs. Titration experiments on NIH-3T3 cells revealed that inclusion of the CD4 silencer in the LTRs did not reduce the titer of the vectors. These findings indicate that a cellular silencer can be successfully included in retroviral vectors, where it maintains its transcription-regulatory function, thus suggesting a novel approach to transcriptional targeting.
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