2. Academic Validation
  3. Influenza A Virus (H1N1) Infection Induces Glycolysis to Facilitate Viral Replication

Influenza A Virus (H1N1) Infection Induces Glycolysis to Facilitate Viral Replication

  • Virol Sin. 2021 Dec;36(6):1532-1542. doi: 10.1007/s12250-021-00433-4.
Lehao Ren  # 1 2,  Wanju Zhang  # 3,  Jing Zhang  # 4,  Jiaxiang Zhang 1,  Huiying Zhang 5,  Yong Zhu 1,  Xiaoxiao Meng 1,  Zhigang Yi 6,  Ruilan Wang 7
Affiliations

Affiliations

  • 1 Department of Emergency and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
  • 2 Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 3 Microbiology Laboratory, Shanghai Municipal Centre for Disease Control and Prevention, Shanghai, 200336, China.
  • 4 Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • 5 Department of Pathogen Diagnosis and Biosafety, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China.
  • 6 Department of Pathogen Diagnosis and Biosafety, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China. zgyi@fudan.edu.cn.
  • 7 Department of Emergency and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China. wangyusun@hotmail.com.
  • # Contributed equally.
PMID: 34519916 DOI: 10.1007/s12250-021-00433-4
Abstract

Viruses depend on host cellular metabolism to provide the energy and biosynthetic building blocks required for their replication. In this study, we observed that influenza A virus (H1N1), a single-stranded, negative-sense RNA virus with an eight-segmented genome, enhanced glycolysis both in mouse lung tissues and in human lung epithelial (A549) cells. In detail, the expression of Hexokinase 2 (HK2), the first Enzyme in glycolysis, was upregulated in H1N1-infected A549 cells, and the expression of Pyruvate Kinase M2 (PKM2) and pyruvate dehydrogenase kinase 3 (PDK3) was upregulated in H1N1-infected mouse lung tissues. Pharmacologically inhibiting the glycolytic pathway or targeting hypoxia-inducible factor 1 (HIF-1), the central transcriptional factor critical for glycolysis, significantly reduced H1N1 replication, revealing a requirement for glycolysis during H1N1 Infection. In addition, pharmacologically enhancing the glycolytic pathway further promoted H1N1 replication. Furthermore, the change of H1N1 replication upon glycolysis inhibition or enhancement was independent of interferon signaling. Taken together, these findings suggest that influenza A virus induces the glycolytic pathway and thus facilitates efficient viral replication. This study raises the possibility that metabolic inhibitors, such as those that target glycolysis, could be used to treat influenza A virus Infection in the future.

Keywords

Glycolysis; H1N1; Hypoxia-inducible factor 1 (HIF-1); Interferon; Replication.

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  • HY-15967
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