Hypoxia-inducible factor 1 and its role in viral carcinogenesis.
The advent of modern molecular biology has allowed for the discovery of several mechanisms by which oncoviruses promote carcinogenesis. Remarkably, nearly all human oncogenic viruses increase levels of the transcription factor hypoxia-inducible factor 1 (HIF-1). In this review, we highlight HIF-1׳s significance in viral oncogenesis, while providing an in-depth analysis of its activation mechanisms by the following oncoviruses: human papillomaviruses (HPVs), hepatitis B/C viruses (HBV/HCVs), Epstein-Barr virus (EBV), Kaposi׳s sarcoma-associated herpes virus (KSHV), and human T-cell lymphotropic virus (HTLV-1). We discuss virus-induced HIF-1׳s role in transcriptional upregulation of metabolic, angiogenic, and microenvironmental factors that are integral for oncogenesis. Admittedly, conclusive evidence is lacking as to whether activation of HIF-1 target genes is necessary for malignant transformation or merely a result thereof. In addition, a complete understanding of host-virus interactions, the effect of viral genomic variation, and the clinical (and potential therapeutic) relevance of HIF-1 in viral oncogenesis warrant further investigation.
Probe Development & Biomarker Exploration, Thunder Bay Regional Research Institute, 980 Oliver Rd, Thunder Bay, Ont., Canada P7B 6V4; Department of Biology, Lakehead University, Thunder Bay, Ont., Canada.
Sean
S
Cuninghame
Probe Development & Biomarker Exploration, Thunder Bay Regional Research Institute, 980 Oliver Rd, Thunder Bay, Ont., Canada P7B 6V4; Department of Biology, Lakehead University, Thunder Bay, Ont., Canada.
Robert
R
Jackson
Probe Development & Biomarker Exploration, Thunder Bay Regional Research Institute, 980 Oliver Rd, Thunder Bay, Ont., Canada P7B 6V4; Department of Biology, Lakehead University, Thunder Bay, Ont., Canada. Electronic address: zehbei@tbh.net.
Ingeborg
I
Zehbe
D063646:Carcinogenesis; D002472:Cell Transformation, Viral; D004267:DNA Viruses / Q000502:physiology*; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D012328:RNA Viruses / Q000502:physiology*; D014158:Transcription, Genetic
D051793:Hypoxia-Inducible Factor 1
Angiogenesis; HIF-1; Invasion; Metabolism; Metastasis; Oncoviruses; Tumor microenvironment