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Hypoxia and viral infectious diseases
Richard Huang, … , Eng Eong Ooi, Michael Ohh
Richard Huang, … , Eng Eong Ooi, Michael Ohh
Published April 8, 2021
Citation Information: JCI Insight. 2021;6(7):e147190. https://doi.org/10.1172/jci.insight.147190.
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Hypoxia and viral infectious diseases

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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.

Authors

Richard Huang, Melissa Huestis, Esther Shuyi Gan, Eng Eong Ooi, Michael Ohh

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Figure 1

The canonical oxygen-sensing pathway involving HIF.

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The canonical oxygen-sensing pathway involving HIF.
HIF-1α is regulated ...
HIF-1α is regulated through an oxygen-dependent mechanism that involves the hydroxylation of proline residues by PHDs and essential cofactors (including α-ketoglutarate and iron). Afterward, the E3 ubiquitin ligase complex (comprising VHL, Elongin B/C [EloB/C], Cul2, Rbx1, and E2) ubiquitinates HIF-1α, which results in its proteasomal degradation. However, under hypoxic conditions, PHDs are unable to perform their function, and HIF-1α is able to associate with HIF-1β within the nucleus to initiate the transcriptional responses for hypoxic adaptation.

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