Interferon regulatory factor (IRF)-2 activates the HPV-16 E6–E7 promoter in keratinocytes

Abstract 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...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2010-04, Vol.399 (2), p.270-279
Main Authors: Lace, Michael J, Anson, James R, Haugen, Thomas H, Turek, Lubomir P
Format: Article
Language:English
Subjects:
a-Interferon
Cell Line
Cytokine induction
Feedback
Gene expression
Gene Expression Regulation, Viral
Human papillomavirus 16 - genetics
Humans
Immune response
Immunoevasion
Infectious Disease
Interferon
Interferon regulatory factor
Interferon regulatory factor 1
Interferon regulatory factor 2
Interferon Regulatory Factor-1 - metabolism
Interferon Regulatory Factor-2 - metabolism
IRF
Keratinocyte
Keratinocytes
Keratinocytes - virology
Mucosa
Oncogene Proteins, Viral - genetics
Papillomavirus
Papillomavirus E7 Proteins
Promoter Regions, Genetic
Promoters
Regulatory sequences
Replication
Repressor Proteins - genetics
Signal Transduction
Transcription
Transcription, Genetic
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Summary:Abstract 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.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2009.12.025