Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile , Santiago, Chile.
Departamento De Endocrinología, Facultad De Medicina, Escuela De Medicina, Pontificia Universidad Católica De Chile , Santiago, Chile.
Virulence. 2020 Dec;11(1):1482-1500. doi: 10.1080/21505594.2020.1836904.
Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that plays critical roles during the cellular response to hypoxia. Under normoxic conditions, its function is tightly regulated by the degradation of its alpha subunit (HIF-1α), which impairs the formation of an active heterodimer in the nucleus that otherwise regulates the expression of numerous genes. Importantly, HIF-1 participates in both cancer and infectious diseases unveiling new therapeutic targets for those ailments. Here, we discuss aspects related to the activation of HIF-1, the effects of this transcription factor over immune system components, as well as the involvement of HIF-1 activity in response to viral infections in humans. Although HIF-1 is currently being assessed in numerous clinical settings as a potential therapy for different diseases, up to date, there are no clinical studies evaluating the pharmacological modulation of this transcription factor as a possible new antiviral treatment. However, based on the available evidence, clinical trials targeting this molecule are likely to occur soon. In this review we discuss the role of HIF-1 in viral immunity, the modulation of HIF-1 by different types of viruses, as well as the effects of HIF-1 over their life cycle and the potential use of HIF-1 as a new target for the treatment of viral infections.
缺氧诱导因子 1(HIF-1)是一种转录因子,在细胞对缺氧的反应中起着关键作用。在正常氧条件下,其功能受到其α亚基(HIF-1α)降解的严格调节,这会损害在核中形成活性异二聚体的能力,否则该异二聚体将调节许多基因的表达。重要的是,HIF-1 参与癌症和传染病,为这些疾病揭示了新的治疗靶点。在这里,我们讨论了与 HIF-1 的激活相关的方面,该转录因子对免疫系统成分的影响,以及 HIF-1 活性在人类对病毒感染的反应中的参与。虽然 HIF-1 目前正在许多临床环境中作为治疗不同疾病的潜在疗法进行评估,但迄今为止,尚无评估该转录因子药理学调节作为潜在新抗病毒治疗的临床研究。然而,基于现有证据,针对该分子的临床试验很可能很快就会进行。在这篇综述中,我们讨论了 HIF-1 在病毒免疫中的作用、不同类型的病毒对 HIF-1 的调节作用,以及 HIF-1 对其生命周期的影响,以及将 HIF-1 用作治疗病毒感染的新靶点的潜在用途。