Interferon regulatory factor (IRF)-2 activates the HPV-16 E6-E7 promoter in keratinocytes.
Interferon regulatory factors (IRFs) are critical mediators of gene expression, cell growth and immune responses. We previously demonstrated that interferon (IFN) induction of early viral transcription and replication in several mucosal HPVs requires IRF-1 binding to a conserved interferon response element (IRE). Here we show that the IRF-2 protein serves as a baseline transactivator of the HPV-16 major early promoter, P97. Cotransfections in IRF knockout cells confirmed that basal HPV-16 promoter activity was supported by both IRF-1 and IRF-2 complexes interacting with the promoter-proximal IRE in a dose-dependent manner. Furthermore, HPV-16 E7 expression downregulates the IRF-2 promoter, thus linking IRF-2 levels to viral transforming gene expression through a negative feedback mechanism. Taken together, these observations reveal a complex viral strategy utilizing multiple signal transduction pathways during the establishment and maintenance of HPV persistence.
Lace
Michael J
MJ
Department of Pathology, VAMC, University of Iowa, Iowa City, IA 52242, USA. michael-lace@uiowa.edu
Anson
James R
JR
Haugen
Thomas H
TH
Turek
Lubomir P
LP
D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism; D050836:Interferon Regulatory Factor-2 / Q000378:metabolism*; D015603:Keratinocytes / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics*; D015398:Signal Transduction; D014158:Transcription, Genetic
C068651:E6 protein, Human papillomavirus type 16; C494257:IRF1 protein, human; C494229:IRF2 protein, human; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16