As new influenza virus strains emerge, finding new mechanisms to control viral infection is imperative. We have found that we can control influenza infection of mammalian cells by altering the level of glucose given to cells. Higher glucose concentrations induce a dose-specific increase in influenza infection. Linking influenza virus infection with glycolysis (the first stage of glucose metabolism), we found that viral replication was significantly reduced after cells were treated with chemical inhibitors of glycolysis. The addition of extracellular ATP after glycolytic inhibition restores influenza infection. We have also determined that higher levels of glucose promoted the assembly of the vacuolar-type ATPase (a proton pump), and increased vacuolar-type ATPase proton-transport activity. We found that the increase of viral infection via high glucose levels could also be reversed by inhibition of this proton pump, linking glucose metabolism, vacuolar-type ATPase activity, and influenza viral infection. Taken together, we propose that altering glucose metabolism may be a potential new approach to inhibit influenza viral infection. (1)
In addition, we are targeting specific subunits of the proton pump, to fine tune-inhibition of Influenza virus infection. We find that the most useful approach to limiting the proton pump’s activity, while maintaining cellular functioning, is to knockdown levels of the subunit V1A. (2)
