Fig. 7.

Diagram of the mechanism by which HIF-1α promotes glycolysis during H1N1-induced severe pneumonia. HIF-1α activation in alveolar epithelial cells promotes the expression of the key glycolytic enzyme HK2 after H1N1 infection and induces a shift in host cell glucose metabolism to glycolysis. On the one hand, this shift provides energy for viral replication. On the other hand, the lactate produced via glycolysis can directly target and bind to MAVS, abolish the mitochondrial localization of MAVS and the formation of the MAVS/RIG-I complex, inhibit downstream IFN-α/β production and block the host cell innate immune response, further increasing viral replication and pathogenicity. Finally, the continuous uncontrollable cytokine storm aggravates lung damage and leads to severe pneumonia.