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Influenza A virus (H1N1) triggers a hypoxic response by stabilizing hypoxia-inducible factor-1α via inhibition of proteasome

tetano

Editor, Senior Moderator
Virology. 2019 Feb 11;530:51-58. doi: 10.1016/j.virol.2019.02.010. [Epub ahead of print]
[h=1]Influenza A virus (H1N1) triggers a hypoxic response by stabilizing hypoxia-inducible factor-1α via inhibition of proteasome.[/h] Ren L[SUP]1[/SUP], Zhang W[SUP]2[/SUP], Han P[SUP]1[/SUP], Zhang J[SUP]1[/SUP], Zhu Y[SUP]1[/SUP], Meng X[SUP]1[/SUP], Zhang J[SUP]3[/SUP], Hu Y[SUP]2[/SUP], Yi Z[SUP]2[/SUP], Wang R[SUP]4[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] Virus reprogramming of host cellular function is a critical strategy for viral survival and replication. A better understanding of virus-host interaction may provide new potential avenues for the treatment of viral diseases. It has been reported that hypoxia-inducible factor-1 (HIF-1) pathway is activated by a range of pathogens via different mechanisms, but the impact of Influenza A virus on HIF-1 signaling is still unclear. In this study, we observed H1N1 infection stabilized HIF-1α under normoxic conditions. In detail, H1N1 did not increase HIF-1α mRNA transcription, nor impaired posttranslational prolyl hydroxylation or ubiquitination of HIF-1α, but inhibited the function of proteasome, resulting in HIF-1α accumulation. Furthermore, a decreased expression of factor inhibiting HIF-1 (FIH-1), which hydroxylates asparagine 803 within HIF-1α to repress HIF-1α activity, was seen after H1N1 infection. Taken together, these findings reveal a previously unrecognized mechanism of viral activation of the HIF-1 pathway, resembling a hypoxic response in normoxia.
Copyright ? 2019 The Authors. Published by Elsevier Inc. All rights reserved.


[h=4]KEYWORDS:[/h] Factor inhibiting HIF-1; H1N1; Hypoxia-inducible factor-1; Proteasome

PMID: 30780125 DOI: 10.1016/j.virol.2019.02.010
 
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