PMID- 30780125
OWN - NLM
STAT- MEDLINE
DCOM- 20190822
LR  - 20190822
IS  - 1096-0341 (Electronic)
IS  - 0042-6822 (Linking)
VI  - 530
DP  - 2019 Apr
TI  - Influenza A virus (H1N1) triggers a hypoxic response by stabilizing 
      hypoxia-inducible factor-1alpha via inhibition of proteasome.
PG  - 51-58
LID - S0042-6822(19)30050-9 [pii]
LID - 10.1016/j.virol.2019.02.010 [doi]
AB  - 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-1alpha under normoxic conditions. In detail, H1N1 did not increase 
      HIF-1alpha mRNA transcription, nor impaired posttranslational prolyl hydroxylation or 
      ubiquitination of HIF-1alpha, but inhibited the function of proteasome, resulting in 
      HIF-1alpha accumulation. Furthermore, a decreased expression of factor inhibiting 
      HIF-1 (FIH-1), which hydroxylates asparagine 803 within HIF-1alpha to repress HIF-1alpha 
      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.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Ren, Lehao
AU  - Ren L
AD  - Department of Critical Care Medicine, Shanghai General Hospital, Shanghai 
      Jiaotong University School of Medicine, Shanghai 201620, China.
FAU - Zhang, Wanju
AU  - Zhang W
AD  - 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.
FAU - Han, Peng
AU  - Han P
AD  - Department of Critical Care Medicine, Shanghai General Hospital, Shanghai 
      Jiaotong University School of Medicine, Shanghai 201620, China.
FAU - Zhang, Jiaxiang
AU  - Zhang J
AD  - Department of Critical Care Medicine, Shanghai General Hospital, Shanghai 
      Jiaotong University School of Medicine, Shanghai 201620, China.
FAU - Zhu, Yong
AU  - Zhu Y
AD  - Department of Critical Care Medicine, Shanghai General Hospital, Shanghai 
      Jiaotong University School of Medicine, Shanghai 201620, China.
FAU - Meng, Xiaoxiao
AU  - Meng X
AD  - Department of Critical Care Medicine, Shanghai General Hospital, Shanghai 
      Jiaotong University School of Medicine, Shanghai 201620, China.
FAU - Zhang, Jing
AU  - Zhang J
AD  - Department of respiratory and critical care medicine, The Fifth People's Hospital 
      of Shanghai, Fudan University, Shanghai 200240, China.
FAU - Hu, Yunwen
AU  - Hu Y
AD  - 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.
FAU - Yi, Zhigang
AU  - Yi Z
AD  - 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.
FAU - Wang, Ruilan
AU  - Wang R
AD  - Department of Critical Care Medicine, Shanghai General Hospital, Shanghai 
      Jiaotong University School of Medicine, Shanghai 201620, China. Electronic 
      address: wangyusun@hotmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190211
PL  - United States
TA  - Virology
JT  - Virology
JID - 0110674
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
MH  - A549 Cells
MH  - *Host-Pathogen Interactions
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Influenza A Virus, H1N1 Subtype/*growth & development
MH  - Proteasome Endopeptidase Complex/*metabolism
MH  - Protein Stability
MH  - Proteolysis
OTO - NOTNLM
OT  - Factor inhibiting HIF-1
OT  - H1N1
OT  - Hypoxia-inducible factor-1
OT  - Proteasome
EDAT- 2019/02/20 06:00
MHDA- 2019/08/23 06:00
CRDT- 2019/02/20 06:00
PHST- 2018/11/23 00:00 [received]
PHST- 2019/02/08 00:00 [revised]
PHST- 2019/02/10 00:00 [accepted]
PHST- 2019/02/20 06:00 [pubmed]
PHST- 2019/08/23 06:00 [medline]
PHST- 2019/02/20 06:00 [entrez]
AID - S0042-6822(19)30050-9 [pii]
AID - 10.1016/j.virol.2019.02.010 [doi]
PST - ppublish
SO  - Virology. 2019 Apr;530:51-58. doi: 10.1016/j.virol.2019.02.010. Epub 2019 Feb 11.