PFKFB3-driven glycolysis determines virus replication and excessive inflammation

  1. Shuofeng Yuan
  2. Ronghui Liang
  3. Yaoming Jin
  4. Sihang Cao
  5. Zi-Wei Ye
  6. Min Guo
  7. Wenxin Zhang
  8. Hehe Cao
  9. Cuiting Luo
  10. Peng Luo
  11. Tao Ni
  12. Hin Chu
  13. Jasper Chan
  14. Dong-Yan Jin
  15. Daming Zuo
  16. Hongbo Zhou
  17. Kwok-Yung Yuen

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Abstract

Novel interventions for 'delayed' presentation by patients with acute respiratory virus diseases are urgently needed to overcome the high viral burden and severe tissue inflammation. Glucose metabolism plays a central role in fueling virus replication and mediating inflammation and immunity. The host enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) is a critical engine that controls the rate of glycolysis. Viral components, such as Influenza A(H1N1) virus PB1 and SARS-CoV-2 Nsp1, can cause PFKFB3 SUMOylation to promote glycolysis, which may serve as a common mechanism to hijack host energy production. PFKFB3 SUMOylation also reprograms host bradykinin signaling with proinflammatory effect via its metabolite fructose 2,6-bisphosphate, which is independent of its proviral activity. Hospitalized flu patients exhibited higher plasma bradykinin than that of healthy donors. Therapy targeting PFKFB3 renders better mice protection than delayed oseltamivir treatment in vivo. Metabolic rewiring of PFKFB3-bradykinin axis can provide a combinatorial therapeutic target for mitigating viral replication and the associated tissue damage by a panel of respiratory viruses.

Article activity feed

  1. Rapid Reviews Infectious Diseases

    Anonymous

    Review 2: "PFKFB3-Driven Glycolysis Determines Virus Replication and Excessive Inflammation"

    Reviewers agreed that the research is “potentially informative” but requires major revision, improved organization, and stronger mechanistic validation to achieve scientific credibility.

  2. Rapid Reviews Infectious Diseases

    Amy Adamson, Eric Daly

    Review 1: "PFKFB3-Driven Glycolysis Determines Virus Replication and Excessive Inflammation"

    Reviewers agreed that the research is “potentially informative” but requires major revision, improved organization, and stronger mechanistic validation to achieve scientific credibility.

  4. Version published to 10.21203/rs.3.rs-6694201/v1 on Research Square