Dr. Adamson and Kohio boosted glucose concentrations in the laboratory cell cultures, and influenza infection rate concomitantly increased. Treating the viral cells with a chemical that inhibits glucose metabolism significantly decreased viral replication in the lab cultures. The researchers also demonstrated that the infection could be restored to high levels simply by adding ATP, the major source of energy for cellular reactions, bypassing the need for glucose.
Looking closer, they discovered that higher levels of glucose promoted the assembly of the V-ATPase proton pump that drives the release of the influenza A genome into the cytoplasm, the internal watery environment of the cell.
When Dr. Adamson and Kohio added the glucose inhibitor to the cell cultures, the assembly of the molecular pump was suppressed. Viral infection, they concluded, was closely tied to the assembly of the V-ATPase pump, and this dependence could be used to manipulate infection success.
Specifically, they were able to suppress viral infection of cells by dismantling the V-ATPase through the lowering of glucose levels. In addition, they inhibited infection by treating cells with chemical inhibitors of glycolysis, the initial pathway of glucose catabolism. Conversely, influenza viral infection of cells could be increased by giving cells more glucose than normal, the researchers report in the journal Virology, http://www.ncbi.nlm.nih.gov/pubmed/23876457.
The ease with which the researchers could dial viral infection down by controlling glucose levels and thus V-ATPase activity suggested a new strategy for throttling influenza viral infection.
"Taken together, we propose that altering glucose metabol
|Contact: Cathy Yarbrough