NF-kappaB cis-acting motifs of the human immunodeficiency virus (HIV) long terminal repeat regulate HIV transcription in human macrophages.
The role of NF-kappaB in the reactivation of human immunodeficiency virus (HIV) from latency in CD4 T lymphocytes is well documented. However, its role in driving HIV transcription in human macrophages, which contain a constitutive nuclear pool of NF-kappaB, is less well understood. In this study we have investigated the role that the constitutive pool of NF-kappaB and the NF-kappaB cis-acting motifs of the HIV long terminal repeat (LTR) play in regulating HIV transcription in human monocytic cells and primary macrophages. Inhibition of the constitutive nuclear pool of NF-kappaB (RelA and RelB) in the promonocytic U937 cell line using dominant-negative IkappaBalpha significantly decreases HIV replication. Moreover, it is demonstrated that in the differentiated monocytic cell line THP1, which contains a constitutive nuclear pool of NF-kappaB (RelB),an HIV provirus containing mutations of the kappaB cis-acting sites in the LTR is transcriptionally impaired. Reduction of the constitutive pool of NF-kappaB in human macrophages by an adenovirus vector expressing a dominant-negative IkappaBalpha also reduces HIV transcription. Lastly, mutation of the NF-kappaB cis-acting sites in the LTR of an R5 HIV provirus completely abrogates the first cycle of HIV transcription. These studies indicate that the cis-acting NF-kappaB motifs of the HIV LTR are critical in initiating HIV transcription in human macrophages and suggest that the constitutive nuclear pool of NF-kappaB is important in regulating HIV transcription in these cells.
Asin
S
S
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Bren
G D
GD
Carmona
E M
EM
Solan
N J
NJ
Paya
C V
CV
D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism; D006678:HIV / Q000235:genetics* / Q000502:physiology; D016325:HIV Long Terminal Repeat; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000821:virology*; D016328:NF-kappa B / Q000378:metabolism*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D012367:RNA, Viral / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D020298:U937 Cells; D014779:Virus Replication / Q000235:genetics
D017931:DNA Primers; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D012367:RNA, Viral; D014157:Transcription Factors