Mutational analysis of sodium butyrate inducible elements in the human immunodeficiency virus type I long terminal repeat.
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.
Bohan
C A
CA
Department of Pathology, Emory University School of Medicine, Atlanta, Georgia 30322.
Robinson
R A
RA
Luciw
P A
PA
Srinivasan
A
A
D001483:Base Sequence; D015152:Blotting, Northern; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002460:Cell Line; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D015498:HIV-2 / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010957:Plasmids; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D015533:Transcriptional Activation; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects
D002087:Butyrates; D004279:DNA, Viral; D012367:RNA, Viral; D020148:Butyric Acid