Regulation of the visna virus long terminal repeat in macrophages involves cellular factors that bind sequences containing AP-1 sites.
Visna virus gene expression is highly restricted in monocytes but is induced by monocyte-macrophage differentiation in vivo. Deletion and linker-scanning mutants, gel shift assays, and DNase I footprinting were used to identify sequences in the visna virus long terminal repeat involved in the developmental regulation of gene expression in the U937 monocytic cell line. We found that an AP-1 and an AP-4 binding site were critical for basal activity and that the AP-1 site was required for phorbol ester-inducible gene expression. These results suggest that cellular factors that interact with AP-1 sites are involved in the developmental regulation of visna virus gene expression in macrophages.
Gabuzda
D H
DH
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Hess
J L
JL
Small
J A
JA
Clements
J E
JE
D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002872:Chromosome Deletion; D004279:DNA, Viral / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003850:Deoxyribonuclease I; D005786:Gene Expression Regulation; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000382:microbiology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000382:microbiology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D012209:Rhabdoviridae / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate; D014157:Transcription Factors / Q000378:metabolism*; D014790:Visna-maedi virus / Q000235:genetics*
D004279:DNA, Viral; D004268:DNA-Binding Proteins; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D014157:Transcription Factors; D003850:Deoxyribonuclease I; D013755:Tetradecanoylphorbol Acetate