Slouched on the uncomfortable chair, wondering if he is going to die and wishing he would, the wary traveler and his tiny stomachal stowaway await the boarding call.
His bleak and vacant stare resting on the ceiling, the soul ringing of the emptiness that only a matching absence in the gastrointestinal tract can bring, he ponders: ‘does travelling with the stomach flu qualifies as “in flight entertainment”’.
Inside, he knows, the viral particles are lining his mucosal membrane and, like nanoscopic Mata-Hari, proteic arches extend from the viral envelope to meet the HBGA receptors of his own cell in an ephemerous and mercenary embrace. In rersponse, the membrane reacts by curving into itself. The virus is lowered into a pit until the vacuole buds off on the inner side of the membrane. There, the capsid changes in a way as yet unknown that allows it to fuze with the membrane of the surrounding vacuole spilling into the cytoplasm beyond the content of the viral capsid including a single tiny thread of ribonuceoic acid. Once inside, the viral VPg protein acts as an adaptor and binds the host’s translation initiation factors, allowing the expression of the viral genome.
Now, here is where it gets even cooler. As mentioned, this viral genome is preposterously small and only contain little genetic information. But Norovirii have a neat little trick up their genomic sleeves…
See, somewhere on the gene’s sequence, additional initiation sequences are present. Normally, binding of the ribosomes at these locations would not be strong enough to start transcription.
Nonetheless, sometime, the transcription is interrupted and the ribosome start disassembling. Yet, having slided alongside the RNA it is close enough from the second initiation site that it is able to reassemble there and start the transcription again.
That is termed ‘Translational termination-re-initiation’ and, in effect, allows for the creation of multiple protein sequences from one single RNA. Now, these sequences still are quite similar, but its shortening allows for enough difference during the folding process as for the proteins to fulfill different functions.
Now, at this point, the virus is multiplying actively in the host cell’s as virus so like to do.
When looking at the gut, we see a marked resorption of the microvilli: essentially, the gut is normally like some soft tube that would have been compressed to fit into a smaller diameter. It’s all folded on itself which allows for a much higher contact surface with the content of the intestine. At a lower scale, the membrane of the individual do the same, protruding into what is called ‘brush border’ to increase its surface of contact.
Each one of these folds is called a microvilli and the infection leads to the shortening of these villis, hence, the reduction of the contact surface.
We don’t really yet understand how the virus cause this reabsorption, it might have to do with a rearrangement of the cell’s cytoskeleton but, what we know, from a study last published August, is that infection can reduce the villus surface area by 47%.
This reduction in itself leads to a reduction in the gut potential to absorb nutrient and, because the concentration in solutes remain so high, water flows into the lumen according to the concentration gradient. That in itself can cause what is termed ‘osmotic diarrhea’.
Furthermore, we now know that the infection leads to apoptosis that causes breaks in the barrier, leading to a flow of water through these breaks. Finally, it seems like the secretion of anion into the lumen is simulated by infection, through mechanism as yet unknown, compounding the osmotic diarrhea.
These factors converge, in a messy exercise of fitness, in the accumulation of virus loaded fluids within the intestinal lumen that is quickly evacuated, shedding the virus into the environment, more precisely on my in-flight neighbor if he doesn’t stop jamming his elbow in my, oh so tender, right flank.
Interestingly, despite Norovirus importance as a human pathogen, many of these details are just now being discovered. We can not grow the virus in culture, which has slowed its discovery and make studying it difficult. Still, a similar virus has recently been discovered in mice that is cultivable and seems to constitute a good model so, new avenues are opening in the study of this not so silent killer.
And that, my friends, promise many very cool findings. Still, would it kill the pilot not to shake this goddamn plane so goddamn much?
