Expression of the human immunodeficiency virus type 1 (HIV-1) provirus in T lymphocytic and monocytic cells can be induced by treatment with hexamethylene bisacetamide (HMBA). The induction occurs at the transcriptional level within 1 to 3 h after the addition of the drug, and is not associated with detectable changes in the binding of transcription factors to the enhancer, TATA box or other regulatory regions of the HIV-1 long terminal repeat (LTR). Using the 5′ deletion mutants of HIV-1 LTR controlling the expression of the chloramphenicol acetyltransferase gene, we found that the deletion of the κB enhancer did not affect HIV-1 inducibility, whereas the deletion of the Sp1 binding sites abolished transcriptional activation. However, the presence of the HIV-1 LTR Sp1 binding sites in the context of the heterologous promoter did not induce responsiveness to HMBA. We conclude that HMBA increases transcription through the secondary modification of the basal transcription complex suggesting the existence of a regulatory pathway that circumvents the requirement for the induction of NF-κB or other DNA-specific binding proteins.
BernsteinD.,
KappesJ. C.1988; Enhanced in vitro reactivation of latent herpes simplex virus from neural and peripheral tissues with hexamethylenebisacetamide. Archives of Virology 99:57–65
CampbellP. L.,
KulozikA. E.,
WoodhamJ. P.,
JonesR. W.1990; Induction by HMBA and DMSO of genes introduced into mouse erythroleukemia and other cell lines by transient transfection. Genes and Development 4:1252–1266
ClouseK. A.,
PowellD.,
WashingtonI.,
PoliG.,
StrebelK.,
FarrarW.,
BarstadP.,
KovaczJ.,
FauciA. S.,
FolksT. M.1989; Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T-cell line. Journal of Immunology 142:431–138
FeinbergM. B.,
BaltimoreD.,
FrankelA. D.1991; The role of Tat in the human immunodeficiency virus life cycle indicates a primary effect on transcriptional elongation. Proceedings of the National Academy of Sciences, U,. S,. A 88:4045–1049
FolksT.,
BennS.,
RabsonA.,
TheodoreT.,
HogganM. D.,
MartinM.,
LightfooteM.,
SellK.1985; Characterization of continuous T-cell line susceptible to the cytopathic effects of the acquired immunodeficiency syndrome (AIDS)-associated retrovirus. Proceedings of the National Academy of Sciences, U,. S,. A 82:4539–1543
FolksT. M.,
JustementJ.,
KinterA.,
SchnittmanS.,
Oren-steinJ.1988; Characterization of a promonocyte clone chronically infected with HIV and inducible by phorbol 13-myristate-12-acetate. Journal of Immunology 140:1117–1122
GarciaJ. A.,
WuF. K.,
MitsuyasuR.,
GaynorR. B.1987; Interactions of cellular proteins involved in the transcriptional regulation of the human immunodeficiency virus. EMBO Journal 6:3761–3770
GazittY.,
ReubenR. C.,
DeitchA. D.,
MarksP. A.,
RifkindR. A.1978; Changes in cyclic adenosine 3′:5′-monophosphate levels during induction of differentiation in murine erythroleukemia cells. Cancer Research 38:3779–3783
GormanC. M.,
MoffatL. F.,
HowardB. H.1982; Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Molecular and Cellular Biology 2:1044–1051
HauberJ.,
CullenB. R.1988; Mutational analysis of the transactivation-responsive region of the human immunodeficiency virus type 1 long terminal repeat. Journal of Virology 62:673–679
JonesK. A.,
LuciwP. A.,
DuchangeN.1988; Structural arrangements of transcription control domains within the 5′-untranslated leader regions of the HIV-1 and HIV-2 promoters. Genes and Development 2:1101–1114
LeibD. A.,
CoenD. M.,
BogardC. L.,
HicksK. A.,
YagerD. R.,
KnipeD. M.,
TylerK. L.,
ShafferP. A.1989; Immediate-early regulatory gene mutants define different stages in the establishment and reactivation of herpes simplex virus latency. Journal of Virology 63:759–768
LeonardJ.,
ParrottC.,
Buckler-WhiteA. J.,
TurnerW.,
RossE. K.,
MartinM. A.,
RabsonA. B.1989; The NF-κB binding sites in the human immunodeficiency virus type 1 long terminal repeat are not required for virus infectivity. Journal of Virology 63:4919–4924
LiC.,
LaiC.,
SigmanD. S.,
GaynorR. B.1991; Cloning of a cellular factor, interleukin binding factor, that binds to NFAT-like motifs in the human immunodeficiency virus long terminal repeat. Proceedings of the National Academy of Sciences, U,. S,. A 88:7739–7743
LuckowB.,
SchutzG.1987; CAT constructions with unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Research 13:5490
McFarlaneM.,
DaksisJ. I.,
PrestonC. M.1992; Hexamethyl-ene bisacetamide stimulates herpes simplex virus immediate early gene expression in the absence of trans-induction by Vmw65. Journal of General Virology 73:285–292
MarksP. A.,
RifkindD. A.1989; Induced differentiation of erythroleukemia cells by hexamethylene bisacetamide: a model for cytodifferentiation of transformed cells. Environmental Health Perspectives 80:181–188
MelloniE.,
PontremoliS.,
MichettiM.,
SaccoO.,
CakirogluA. G.,
JacksonJ. F.,
RifkindR. A.,
MarksP. A.1987; Protein kinase C activity and hexamethylenebisaeetamide-induced erythroleukemia cell differentiation. Proceedings of the National Academy of Sciences, U,. S,. A 84:5282–5286
MoscaJ. D.,
BednarikD. P.,
RajN. B. K.,
RosenC. A.,
SodroskiJ. G.,
HaseltineW. A.,
HaywardG. S.,
PithaP. M.1987; Activation of human immunodeficiency virus by herpesvirus infection: identification of a region within the long terminal repeat that responds to a trans acting factor encoded by herpes simplex virus 1. Proceedings of the National Academy of Sciences, U. S. A. 84:7408–7412
NabelG.,
BaltimoreD.1987; An inducible transcription factor activates expression of human immunodeficiency virus in T-cells. Nature, London 326:711–713
PopikW.,
PithaP. M.1993; Role of tumor necrosis factor alpha in activation and replication of the tat-defective human immunodeficiency virus type 1. Journal of Virology 67:1094–1099
RamsayR. G.,
IkedaK.,
RifkindR. A.,
MarksP. A.1986; Changes in gene expression associated with induced differentiation of erythroleukemia: proto-oncogenes, globin genes and cell division. Proceedings of the National Academy of Sciences, U,. S,. A 83:6849–6853
RobertsM. S.,
BoundyA.,
O’HareP.,
PizzornoM. C.,
CiufoD. M.,
HaywardG. S.1988; Direct correlation between a negative autoregulatory response element at the cap site of the herpes simplex virus type 1 IE175 (α4) promoter and a specific binding site for the IE175 (ICP4) protein. Journal of Virology 62:4307–4320
RosenC. A.,
SodroskiJ. G.,
HaseltineW. A.1985; The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat. Cell 41:813–823
RossE. K.,
Buckler-WhiteA. J.,
RabsonA. B.,
EnglundG.,
MartinM. A.1991; Contribution of NF-κB and Sp1 binding motifs to the replicative capacity of human immunodeficiency virus type 1: distinct patterns of viral growth are determined by T-cell types. Journal of Virology 65:4350–4358
SakaguchiM.,
Zenzie-GregoryB.,
GroopmanJ. E.,
SmaleS. T.,
KimS.1991; Alternative pathway for production of human immunodeficiency virus gene expression: involvement of the general transcription machinery. Journal of Virology 65:5448–5456
ShawJ. P.,
UtzP. J.,
DurandD. B.,
TouleJ. J.,
EmmelE. A.,
CrabtreeG. R.1988; Identification of putative regulator of early T cell activation genes. Science 241:202–203
SmithM. R.,
GreeneW. R.1989; The same 50-kDa cellular protein binds to the negative regulatory elements of the interleukin 2 receptor a-chain gene and the human immunodeficiency virus type 1 long terminal repeat. Proceedings of the National Academy of Sciences, U,. S,. A 86:8526–8530
SouthgateC. D.,
GreenM. R.1991; The HIV-1 Tat protein activates transcription from an upstream DNA-binding site: implications for Tat function. Genes and Development 5:2496–2507
Tong-StarksenS. E.,
LuciwP. A.,
PeterlinB. M.1987; Human immunodeficiency virus long terminal repeat responds to T-cell activation signals. Proceedings of the National Academy of Sciences, U,. S,. A 84:6845–6849
VlachJ.,
PithaP. M.1992a; Herpes simplex virus type 1-mediated induction of human immunodeficiency virus type 1 provirus correlates with binding of nuclear proteins to the NF-κB enhancer and leader sequence. Journal of Virology 66:3616–3623
VlachJ.,
PithaP. M.1992b; Activation of human immunodeficiency type 1 provirus in T-cells and macrophages is associated with induction of inducer-specific NF-κB binding proteins. Virology 187:63–72
WhitbyA. J.,
BlythW. A.,
HillT. J.1987; The effect of DNA hypomethylating agents on the reactivation of herpes simplex virus immediate early gene expression. Genes and Development 2:718–729
WuF. K.,
GarciaJ. A.,
HarrichD.,
GaynorR. B.1988; Purification of the human immunodeficiency virus type 1 enhancer and TAR binding proteins EBP-1 and UBP-1. EMBO Journal 7:2117–2129
ZeichnerS. L.,
HirkaG.,
AndrewsP. W.,
AlwineJ. C.1992; Differentiation-dependent human immunodeficiency virus long terminal repeat regulatory elements active in human teratocarcinoma cells. Journal of Virology 66:2268–2273