Modulation of HIV‐1 enhancer activity and virus production by cAMP

FEBS Letters

Banas, Brigitte¹  Eberle, Josef²  Banas, Bernhard¹  Schlöndorff, Detlef¹  Luckow, Bruno¹ 

[1] Medizinische Poliklinik, Ludwig-Maximilians-Universität München, Molekulare Infektiologie, Pettenkoferstraße 8a, D-80336 Munich, Germany;Max-von-Pettenkofer-Institut, Virologie, Ludwig-Maximilians-Universität München, Pettenkoferstraße 9a, D-80336 Munich, Germany

关键词: HIV-1 enhancer;    cAMP;    Negative regulation;    Transient transfection;    Virus production;    CRE;    cAMP response element;    CREB;    CRE binding protein;    CBP;    CREB binding protein;    HIV;    human immunodeficiency virus;    LTR;    long terminal repeat;    PBLs;    peripheral blood lymphocytes;    PKA;    protein kinase A;    RT;    reverse transcriptase;   

DOI  :  10.1016/S0014-5793(01)03182-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The effect of cAMP on the transcriptional activity of the HIV-1 long terminal repeat/enhancer was investigated and compared to the effect of cAMP on virus replication. In culture cAMP repressed virus replication in vivo using different cell types. Transient transfection studies with HIV-1 enhancer-derived luciferase reporter gene constructs identified the minimal DNA sequence mediating the negative regulatory effect of cAMP on HIV-1 transcription. A single nuclear factor κB element from the HIV-1 enhancer mediates the repressive effect on transcription. AP-2 is not involved in cAMP repression. Stable transfection of Jurkat T cells with the co-activators CREB binding protein (CBP) and p300 completely abolished the cAMP repressive effect, supporting the hypothesis that elevation of intracellular cAMP increases phosphorylation of CREB, which then competes with phosphorylated p65 and Ets-1 for limiting amounts of CBP/p300 thereby mediating the observed repressive effect on transcription. These findings suggest an important role of cAMP on HIV-1 transcription.

【 授权许可】

Unknown