This press release, from 2013, surfaced on twitter (embarrassingly I have again lost the tweeter due a hat tip for this. Mea culpa. Found him, it was resurfaced/retweeted by Guðmundur Jóhannsson).
Glucose: Potential new target for combating annual seasonal flu
which summarises this paper:
Glycolytic control of vacuolar-type ATPase activity: a mechanism to regulate influenza viral infection.
Over the last few weeks I happen to have been immersed in vacuoles/lysosomes, cysteine toxicity, longevity and yeasts. Oh, and mTORC1, which is deeply associated with lysosomes. So I'm in a mindset of how lysosomes/mTOR control longevity/anabolism.
Anyhoo. Influenza A virus uses lysosomes to maximise its survival. My prediction is that it activates mTOR to induce a marked anabolic state and hijacks that anabolic state to generate lots and lots of influenza A virus particles. It will do that, much as a cancer cell might, by aerobic glycolysis working on the basis that glycolysis, while inefficient, is very, very fast at generating ATP compared to OxPhos. This would suggest that the free availability of glucose secondary to hyperglycaemia (or increased access of glucose to the cytoplasm secondary to hyperinsulinaemia) will increase the success of the influenza virus, as found in Kohio's paper.
Which brings us to anabolism and glycolysis. Not only does aerobic glycolysis supply ATP for anabolism faster than OxPhos can but it also supplies phosphoenolpyruvate for amino acid synthesis, plus other anabolic substrates come from glucose via assorted pathways.
However for every glucose molecule which generates a pair of 1-3 bisphosphoglycerate molecules two NAD+ are consumed. If these glycerate molecules are used for anabolism via phosphoenolpyruvate they will not restore the NAD+ balance by converting to lactate. The basic story is in
Cell surface oxygen consumption (2)
Cell surface oxygen consumption (3)
with an introduction to the concept in
Cell surface oxygen consumption (1)
The glycerophosphate shuttle won't do the job because this too is limited to the speed of OxPhos. Cell surface oxygen consumption does fit the bill for rapid restoration of NAD+.
So. Does influenza virus drive cell surface oxygen consumption to facilitate anabolism at a speed fast enough to keep it one step ahead of the innate immune system?
I don't know.
But another standard (primarily rodent) model RNA virus certainly does.
Oxygen uptake associated with Sendai-virus-stimulated chemiluminescence in rat thymocytes contains a significant non-mitochondrial component
I think this will be a basic feature of rapid anabolism, be that viral or neoplasia related.
Will hyperglycaemia and/or hyperinsulinaemia facilitate viral directed anabolism under infection by another, more topical novel human RNA virus?
Personally, I'm not planning on finding out the hard way when I get around to catching the current bug.