Influenza A virus (H1N1) triggers a hypoxic response by stabilizing hypoxia-inducible factor-1α via inhibition of proteasome.
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.
['Ren|Lehao|L|', 'Zhang|Wanju|W|', 'Han|Peng|P|', 'Zhang|Jiaxiang|J|', 'Zhu|Yong|Y|', 'Meng|Xiaoxiao|X|', 'Zhang|Jing|J|', 'Hu|Yunwen|Y|', 'Yi|Zhigang|Z|', 'Wang|Ruilan|R|']
D000072283:A549 Cells D054884:Host-Pathogen Interactions D006801:Humans D051795:Hypoxia-Inducible Factor 1, alpha Subunit D053118:Influenza A Virus, H1N1 Subtype D046988:Proteasome Endopeptidase Complex D055550:Protein Stability D059748:Proteolysis
H1N1 Proteasome Hypoxia-inducible factor-1 Factor inhibiting HIF-1