Bohan C A, Robinson R A, Luciw P A, Srinivasan A
Department of Pathology, Emory University School of Medicine, Atlanta, Georgia 30322.
Virology. 1989 Oct;172(2):573-83. doi: 10.1016/0042-6822(89)90200-6.
Sodium butyrate induces gene expression directed by the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in HeLa cells. Inducible regions of the HIV-1 LTR were elucidated by using 5' and 3' LTR deletion mutants and LTR site-directed mutants within the Sp1 binding sites and the trans-activation responsive (TAR) region. Two LTR regions inducible by sodium butyrate were located: one at -117 to -103 (distal site) and one at -65 to -17 (proximal site). In HeLa cells trans-fected with pZ6neo, a biologically active HIV-1 proviral clone, sodium butyrate stimulated virus production following a 3-day treatment. Inducibility of HIV-1 gene expression by sodium butyrate was unrestricted in many human cell types, including CD4+ lymphoid cells and non-CD+ brain cells and fibroblasts. Additionally, sodium butyrate transiently induced HIV-2 LTR-directed gene expression in HeLa cells. Using the HIV-1SF-2 tat gene cotransfected with pLTR-CAT site-directed TAR mutants in HeLa cells, the boundaries of tat-trans-activation were delineated more precisely. These results suggest that the induction of HIV-1 gene expression is mediated by the interaction of sodium butyrate with cellular transcription factors that bind to the HIV-LTR.
丁酸钠可诱导人免疫缺陷病毒1型（HIV-1）长末端重复序列（LTR）在HeLa细胞中指导基因表达。通过使用5'和3' LTR缺失突变体以及Sp1结合位点和反式激活应答（TAR）区域内的LTR定点突变体，阐明了HIV-1 LTR的可诱导区域。确定了丁酸钠可诱导的两个LTR区域：一个位于-117至-103（远端位点），另一个位于-65至-17（近端位点）。在用具有生物活性的HIV-1前病毒克隆pZ6neo转染的HeLa细胞中，丁酸钠经3天处理后刺激了病毒产生。丁酸钠对HIV-1基因表达的诱导在许多人类细胞类型中不受限制，包括CD4 +淋巴细胞、非CD +脑细胞和成纤维细胞。此外，丁酸钠可在HeLa细胞中瞬时诱导HIV-2 LTR指导的基因表达。在HeLa细胞中使用与pLTR-CAT定点TAR突变体共转染的HIV-1SF-2 tat基因，更精确地划定了tat反式激活的边界。这些结果表明，HIV-1基因表达的诱导是由丁酸钠与结合到HIV-LTR的细胞转录因子相互作用介导的。
