Hypoxia-inducible factor 1 and its role in viral carcinogenesis

Article ID	Journal	Published Year	Pages	File Type
6140138	Virology	2014	14 Pages	PDF

Abstract

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-1×³s 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×³s sarcoma-associated herpes virus (KSHV), and human T-cell lymphotropic virus (HTLV-1). We discuss virus-induced HIF-1×³s 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.

Keywords

PHD mTOR vGPCR ERK HDAC LANA KSHV 4E binding protein 4E-BP LMP LCL GAPDH HHV MNK EBNA AP-1 PGK1 STAT-3 HIF VHL HRE ARNT PFK URR E6-AP ATP/ADP NF-κB PI3K MMP LDHA eIF-4E IKKβ TCA inhibitor of nuclear factor kappa-B kinase subunit beta HBV/HCV ERBB2 SUMO ORF RTK PDK1 HIF-1 E-cadherin HCC MAPK ROS Sp-1 Angiogenesis Akt aryl hydrocarbon receptor nuclear translocator specificity protein-1 EBV Invasion EMT RTK, Receptor tyrosine kinase glucose transporters Tumor suppressor Serine/threonine kinase hypoxia response element Hypoxia-inducible factor Vascular endothelial growth factor Vascular Endothelial Growth Factor (VEGF)nuclear factor kappa-light-chain-enhancer of activated B cells ODD phosphatidylinositol-3-kinase Phosphofructokinase Phosphoglycerate kinase 1 open reading frame lactate dehydrogenase Matrix metalloprotease signal transducer and activator of transcription 3 Metabolism Metastasis MEK Tumor microenvironment upstream regulatory region Huh-7 histone deacetylases human herpes virus Human papillomavirus HPV activator protein-1 mitogen-activated protein kinase Prolyl hydroxylase Pyruvate dehydrogenase kinase 1 Pten Hepatocellular carcinoma small ubiquitin-like modifier extracellular signal-regulated kinase Epithelial–mesenchymal transition glyceraldehyde-3-phosphate dehydrogenase Reactive oxygen species Growth factor receptor