Huang L M, Jeang K T
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
J Virol. 1993 Dec;67(12):6937-44. doi: 10.1128/JVI.67.12.6937-6944.1993.
Expression of the human immunodeficiency virus type 1 (HIV-1) is strongly activated by Tat. The proper action of Tat requires three elements: TATAA, TAR, and upstream motifs in the HIV-1 long terminal repeat. We show here that the correct spatial arrangement among Tat, Sp1, and TATAA crucially influences HIV expression. Under conditions in which basal promoter activity is unperturbed, distancing Sp1 from TATAA markedly affected Tat trans activation. An increase in the Sp1-TATAA distance from 18 to 101 nucleotides (depending on the inserted sequence) rendered HIV-1 either partially or wholly replication defective. This critical dependence on spacing suggests that Tat-, Sp1-, and TATAA-binding factors must correctly contact each other for optimal expression and replication of HIV-1.
人类免疫缺陷病毒1型(HIV-1)的表达受到Tat的强烈激活。Tat的正常作用需要三个元件:TATAA、TAR和HIV-1长末端重复序列中的上游基序。我们在此表明,Tat、Sp1和TATAA之间正确的空间排列对HIV表达至关重要。在基础启动子活性不受干扰的条件下,将Sp1与TATAA拉开距离会显著影响Tat反式激活。Sp1-TATAA距离从18个核苷酸增加到101个核苷酸(取决于插入序列)会使HIV-1部分或完全复制缺陷。对间距的这种关键依赖性表明,Tat、Sp1和TATAA结合因子必须正确相互接触,以实现HIV-1的最佳表达和复制。