Abstract
Oxygen-sensing mechanisms allow cells to adapt and respond to changes in cellular oxygen tension, including hypoxic conditions. Hypoxia-inducible factor (HIF) is a central mediator in this fundamental adaptive response, and has critical functions in normal and disease physiology. Viruses have been shown to manipulate HIFs during their life cycle to facilitate replication and invasion. Conversely, HIFs are also implicated in the development of the host immune system and response to viral infections. Here, we highlight the recent revelations of host-pathogen interactions that involve the hypoxic response pathway and the role of HIF in emerging viral infectious diseases, as well as discussing potential antiviral therapeutic strategies targeting the HIF signaling axis.
Highlights
The cellular environment is in constant flux
prolyl hydroxylases (PHDs) are not active in the absence of oxygen; proline hydroxylation of hypoxia-inducible factor (HIF) is abrogated under hypoxia, allowing it to escape degradation and accumulate within the nucleus to promote the transcription of hypoxia-responsive genes (Figure 1) [1, 2]
HIF was originally discovered as a mediator of oxygen sensing, its role in development has since expanded to areas of research such as viral pathogenesis and immunity [9, 10]
Summary
Oxygen-sensing mechanisms allow cells to adapt and respond to changes in cellular oxygen tension, including hypoxic conditions. Hypoxia-inducible factor (HIF) is a central mediator in this fundamental adaptive response, and has critical functions in normal and disease physiology. HIFs are implicated in the development of the host immune system and response to viral infections. We highlight the recent revelations of host-pathogen interactions that involve the hypoxic response pathway and the role of HIF in emerging viral infectious diseases, as well as discussing potential antiviral therapeutic strategies targeting the HIF signaling axis. Authorship note: RH and MH are co– first authors and contributed to this work. Conflict of interest: The authors have declared that no conflict of interest exists.
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