Tat and the HIV-1 promoter: A model for RNA-mediated regulation of transcription

Sheridan, Philip L.; Sheline, Christian T.; Milocco, Lawrence H.; Jones, Katherine A.

doi:10.1016/1044-5773(93)80010-l

Cited by 13 publications

(7 citation statements)

References 55 publications

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“…The HIV LTR promoter is controlled by a complex enhancer containing several transcription factor binding sites (41). In activated T cells, the basal level of HIV transcription is mainly regulated by a tandem element which contains two NF-B binding sites.…”

Section: Resultsmentioning

confidence: 99%

“…The effector plasmid pcDNA3/73, which we had generated during our initial studies on the identification of LANA (25), contains viral sequences from nucleotide (nt) 127394 to nt 123663 (all nucleotide numbering refers to GenBank sequence no. U75698 [41]). The ORF73 fragment was cloned from a clone as a KpnI/NheI fragment into the KpnI/XbaI sites of the pcDNA3 polylinker (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

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Modulation of Cellular and Viral Gene Expression by the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus

Renne

Barry

Dittmer

et al. 2001

J Virol

193

168

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Kaposi's sarcoma-associated herpesvirus (KSHV), also called human herpesvirus 8 (HHV-8), is the likely etiological agent of Kaposi's sarcoma and primary effusion lymphoma. Common to these malignancies is that tumor cells are latently infected with KSHV. Viral gene expression is limited to a few genes, one of which is the latency-associated nuclear antigen (LANA), the product of ORF73. Examination of the primary sequence of LANA reveals some structural features reminiscent of transcription factors, leading us to hypothesize that LANA may regulate viral and cellular transcription during latency. In reporter gene-based transient transfection assays, we found that LANA can have either positive or negative effects on gene expression. While expression of a reporter gene from several synthetic promoters was increased in the presence of LANA, expression from the human immunodeficiency virus (HIV) long terminal repeat (LTR)-and from NF-Bdependent reporter genes-was reduced by LANA expression. In addition, the promoter of KSHV ORF73 itself is activated up to 5.5-fold by LANA. This autoregulation may be important in tumorigenesis, because two other genes (v-cyclin and v-FLIP) with likely roles in cell growth and survival are also controlled by this element. To identify cellular genes influenced by LANA, we employed cDNA array-based expression profiling. Six known genes (and nine expressed sequence tags) were found to be upregulated in LANA-expressing cell lines. One of these, Staf-50, is known to inhibit expression from the HIV LTR; most of the other known genes are interferon inducible, although the interferon genes themselves were not induced by LANA. These data demonstrate that LANA expression has effects on cellular and viral gene expression. We suggest that, whether direct or indirect in origin, these effects may play important roles in the pathobiology of KSHV infection.Kaposi's sarcoma (KS)-associated herpesvirus (KSHV), also called human herpesvirus 8 (HHV-8), is associated with KS and with two lymphoproliferative diseases: primary effusion lymphomas (PEL) and multicentric Castleman's disease (18). Common to these neoplasms is the fact that the majority of tumor cells are latently infected (5, 46). Viral gene expression in this stage is restricted to a small number of genes, one of which is the latency-associated nuclear antigen (LANA). This antigen was first identified by reactivity with sera from KS patients in immunofluorescence assays (IFA) on latently infected PEL cell lines (19,25). Using Northern blot analysis and expression cloning, it was subsequently shown that LANA is encoded by ORF73 of KSHV (24,26,36). ORF73 encodes a protein of about 1,162 amino acids (aa) and is expressed from a singly spliced mRNA of 5.7 kb which also bears ORF72 and ORF71 coding sequences. In situ hybridization revealed that nearly all cells in the KS lesion express ORF73 mRNA (12), and the expression of LANA protein has been demonstrated by immunohistochemistry in all malignancies associated with KSHV (13).The identification of OR...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Modulation of Cellular and Viral Gene Expression by the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus

Renne

Barry

Dittmer

et al. 2001

J Virol

193

168

View full text Add to dashboard Cite

show abstract

“…4A). Transcription from the HIV-1 LTR is totally dependent on the HIV-1 transcriptional activator tat (Sheridan et al, 1993). If that CAT production was easily detectable from pBSPtatLTRCAT which contains two wild type HPV-16 splice sites (Fig.…”

Section: Plasmids That Amplify the Levels Of Hpv-16 Late Mrnasmentioning

confidence: 99%

Development and validation of a novel reporter assay for human papillomavirus type 16 late gene expression

Orru¹,

Cunniffe²,

Ryan³

et al. 2012

Journal of Virological Methods

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“…TAR is present in the 5Ј untranslated region of all HIV transcripts and minimally extends from residues ϩ14 to ϩ44 relative to the cap site at ϩ1, forming a stem-loop structure that binds Tat as well as cellular factors (33). These interactions between TAR, Tat, and cellular factors increase transcriptional initiation and elongation by RNA polymerase II complexes from the long terminal repeat (LTR) (22,23,38).…”

mentioning

confidence: 99%

Effects of the simian virus 40 origin of replication on transcription from the human immunodeficiency virus type 1 promoter

Nahreini

Mathews

1995

J Virol

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Positive and negative effects of DNA replication on gene transcription have been documented in a variety of systems. We examined the effects of the simian virus 40 (SV40) origin of replication on transcription from the human immunodeficiency virus type 1 (HIV-1) promoter, using a transient expression assay in COS-1 cells. The basal activity and Tat transactivation of the HIV promoter were greatly stimulated by the SV40 origin of replication independent of its position relative to the long terminal repeat. These effects were abolished by mutational inactivation of the SV40 origin and were reduced by a DNA replication inhibitor. The magnitude of promoter activation exceeded the increment expected from the increase in template number resulting from DNA replication. The SV40 T-antigen-induced DNA replication augmented the generation of both processive and nonprocessive HIV long terminal repeat-directed transcripts, and Tat primarily enhanced the initiation of those transcripts that were destined to be efficiently elongated. Our data suggest that the HIV promoter displays greater transcriptional activity on replicative DNA templates. This property may influence the activity of integrated HIV provirus and its transition from latency to productive infection.

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Tat and the HIV-1 promoter: A model for RNA-mediated regulation of transcription

Cited by 13 publications

References 55 publications

Modulation of Cellular and Viral Gene Expression by the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus

Modulation of Cellular and Viral Gene Expression by the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus

Development and validation of a novel reporter assay for human papillomavirus type 16 late gene expression

Effects of the simian virus 40 origin of replication on transcription from the human immunodeficiency virus type 1 promoter

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