A functional interferon regulatory factor-1 (IRF-1)-binding site in the upstream regulatory region (URR) of human papillomavirus type 16.
We recently identified a new enhancer element (HIRE-1, HPV-Interferon Responsive Element-1) in the upstream regulatory region (URR) of human papillomavirus (HPV) type 16. HIRE-1 is located upstream from and in close proximity to the TATA box. HIRE-1 is 1 nt shorter in its 5' sequence in comparison to a consensus IRF-1 binding site (IRF-E). Gel shift analyses clearly demonstrated that HIRE-1 is capable of binding IRF-1 in response to interferon-gamma (IFN-gamma) treatment. In a reporter system, HIRE-1 stimulated transcription in response to IRF-1 or IFN gamma from both a heterologous or the homologous (p97) promoter in a dose-dependent manner. Mutations in the core binding sequence strongly decreased this enhancer activity. Interestingly, HIRE-1 stimulated transcription in the context of the full URR in a cell-type-specific manner, thereby suggesting the role of other cell-type-specific factors that might counteract with its function. Thus, our results may explain the inconsistent clinical and experimental results observed following IFN treatment of cervical lesions or cells. Also, this new enhancer may have an important function during inflammatory responses against HPV type 16.
Arany
Istvan
I
Department of Microbiology, The University of Texas Medical Branch, Galveston, TX 77555-1070, USA. aranyistvan@uams.edu
Grattendick
Kenneth J
KJ
Whitehead
William E
WE
Ember
Istvan A
IA
Tyring
Stephen K
SK
D024506:5' Flanking Region; D001665:Binding Sites; D002461:Cell Line, Transformed; D004279:DNA, Viral; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D006801:Humans; D050835:Interferon Regulatory Factors; D007371:Interferon-gamma / Q000494:pharmacology; D027383:Papillomaviridae / Q000235:genetics*; D010448:Peptide Initiation Factors / Q000378:metabolism; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000378:metabolism*
D004279:DNA, Viral; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D010448:Peptide Initiation Factors; D014157:Transcription Factors; D014764:Viral Proteins; C104836:eukaryotic translational regulator p97; C413486:viral interferon regulatory factors; D007371:Interferon-gamma