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Virology. 2019 Feb 11;530:51-58. doi: 10.1016/j.virol.2019.02.010. [Epub ahead of print]
Influenza A virus (H1N1) triggers a hypoxic response by stabilizing hypoxia-inducible factor-1α via inhibition of proteasome.
Ren L1, Zhang W2, Han P1, Zhang J1, Zhu Y1, Meng X1, Zhang J3, Hu Y2, Yi Z2, Wang R4.
Author information
Abstract
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.
KEYWORDS:
Factor inhibiting HIF-1; H1N1; Hypoxia-inducible factor-1; Proteasome
PMID: 30780125 DOI: 10.1016/j.virol.2019.02.010
Influenza A virus (H1N1) triggers a hypoxic response by stabilizing hypoxia-inducible factor-1α via inhibition of proteasome.
Ren L1, Zhang W2, Han P1, Zhang J1, Zhu Y1, Meng X1, Zhang J3, Hu Y2, Yi Z2, Wang R4.
Author information
Abstract
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.
KEYWORDS:
Factor inhibiting HIF-1; H1N1; Hypoxia-inducible factor-1; Proteasome
PMID: 30780125 DOI: 10.1016/j.virol.2019.02.010