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.
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.
Virology. 2014 May;456-457:370-83. doi: 10.1016/j.virol.2014.02.027. Epub 2014 Apr 1.
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.
现代分子生物学的出现使得人们发现了几种致癌机制，这些机制与致瘤病毒有关。值得注意的是，几乎所有人类致癌病毒都会增加转录因子缺氧诱导因子 1（HIF-1）的水平。在这篇综述中，我们强调了 HIF-1 在病毒致癌中的重要性，并深入分析了以下致癌病毒激活 HIF-1 的机制：人乳头瘤病毒（HPV）、乙型肝炎/丙型肝炎病毒（HBV/HCV）、EB 病毒（EBV）、卡波济肉瘤相关疱疹病毒（KSHV）和人类 T 细胞白血病病毒（HTLV-1）。我们讨论了病毒诱导的 HIF-1 在转录上调代谢、血管生成和微环境因素中的作用，这些因素对于肿瘤发生是必不可少的。诚然，关于 HIF-1 靶基因的激活是否对恶性转化是必需的，或者仅仅是其结果，还缺乏确凿的证据。此外，进一步研究宿主-病毒相互作用、病毒基因组变异的影响以及 HIF-1 在病毒致癌中的临床（和潜在治疗）相关性，对于全面了解 HIF-1 至关重要。
