Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Av. Portugal 49, Santiago E-8330025, Chile.
Departamento de Endocrinología, Facultad de Medicina, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago E-8330025, Chile.
Int J Mol Sci. 2021 Jul 26;22(15):7954. doi: 10.3390/ijms22157954.
Oxygen is essential for aerobic cells, and thus its sensing is critical for the optimal maintenance of vital cellular and tissue processes such as metabolism, pH homeostasis, and angiogenesis, among others. Hypoxia-inducible factors (HIFs) play central roles in oxygen sensing. Under hypoxic conditions, the α subunit of HIFs is stabilized and forms active heterodimers that translocate to the nucleus and regulate the expression of important sets of genes. This process, in turn, will induce several physiological changes intended to adapt to these new and adverse conditions. Over the last decades, numerous studies have reported a close relationship between viral infections and hypoxia. Interestingly, this relation is somewhat bidirectional, with some viruses inducing a hypoxic response to promote their replication, while others inhibit hypoxic cellular responses. Here, we review and discuss the cellular responses to hypoxia and discuss how HIFs can promote a wide range of physiological and transcriptional changes in the cell that modulate numerous human viral infections.
氧气对需氧细胞至关重要,因此其感知对于最佳维持细胞和组织的重要过程至关重要,例如代谢、pH 平衡和血管生成等。缺氧诱导因子 (HIF) 在氧气感知中起着核心作用。在缺氧条件下,HIF 的α亚基稳定并形成活性异二聚体,易位到细胞核并调节重要基因集的表达。这一过程反过来又会诱导几种生理变化,以适应这些新的不利条件。在过去的几十年中,许多研究报告了病毒感染与缺氧之间的密切关系。有趣的是,这种关系有些是双向的,一些病毒诱导缺氧反应以促进其复制,而另一些则抑制缺氧细胞反应。在这里,我们回顾和讨论细胞对缺氧的反应,并讨论 HIF 如何促进细胞中广泛的生理和转录变化,从而调节多种人类病毒感染。