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

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

  • Virology. 2019 Apr;530:51-58. doi: 10.1016/j.virol.2019.02.010.
Lehao Ren 1,  Wanju Zhang 2,  Peng Han 1,  Jiaxiang Zhang 1,  Yong Zhu 1,  Xiaoxiao Meng 1,  Jing Zhang 3,  Yunwen Hu 2,  Zhigang Yi 2,  Ruilan Wang 4
Affiliations

Affiliations

  • 1 Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201620, China.
  • 2 Department of Pathogen Diagnosis and Biosafety, Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Shanghai Medical College, Fudan University, Shanghai 201508, China.
  • 3 Department of respiratory and critical care medicine, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
  • 4 Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201620, China. Electronic address: wangyusun@hotmail.com.
PMID: 30780125 DOI: 10.1016/j.virol.2019.02.010
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.

Keywords

Factor inhibiting HIF-1; H1N1; Hypoxia-inducible factor-1; Proteasome.

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