Re: The Omnidemic Discussion Thread
Several years ago I asked the question 'why do humans seem to prefer to take their flu serotypes serially while the birds take theirs in parallel?'. I can not find the posts now (but I think I discussed it with Prof. Rachinello). The answer was no one knows but it is probably just time. The progenitor of all type A flus probably occurred in water fowl and has had time to diverge in to all the serologically distinct sub-types birds now have.
Zoonotic emergence in humans would have occurred when some outlier in the avian flu constellation happened to emerge that could coincidentally infect a human. Given time, and isolation from avian flus, the new mammalian line should follow the same path it did in the birds, namely gradual diversification into seriologically distinct groups. Before this had time to occur new zoonotic emergences occurred which displaced the old and reset the clock.
Why the new could not co-exist with the old but has - in most cases replaced them - I do not understand but must, it seems to me, lie in the host immune response.
Our immune response in multifaceted having intra-cellular, extra-cellular, innate and adaptive components. My working assumption is that it is the adaptive response that has caused the strain replacements. If we look at this a little more closely almost any area on any viral protein can elicit a response if it becomes 'visible' to the immune system. In practice only certain outward facing areas on the HA and NA proteins meet this criteria in an intact virion so the 'primary antigenic sites' are mostly HA and a few on NA. Other areas become 'visible' during infection when the infected cell initiates apoptosis and flags bits of alien viral material to MHC family proteins on its exterior for immune system identification and antibody production.
In practice it appears that very recent flu infection gives considerable protection against any flu type. This I assume to be due to a large number of memory cells still circulating from these conserved internal proteins. As time degrades the pool of memory cells those secondary site induced cells will become less protective while only the larger numbers of primary site memory cells will continue to circulate in sufficient numbers to be of much help. At this point only a challenge from a similar HA or NA strain will be rebuffed.
This is what I think is going on, then again it may be well wide of the mark.
As a side note I have concerns about the current holy grail of a universal flu vaccine. This would artificially stimulate the same type of response as the 'all flus' protection I described earlier by inducing massive memory cell production to conserved internal protein antigenic sites. The problem is these sites are conserved because they are hidden and not subject to heavy immune response generated selection pressure if one, or more, of these sites is now made antigenically important it will suffer the same fate as all antibiotics/antivirals/vaccines - induced resistance. The highly variable primary antiviral sites are variable because change helps evade the immune response, if you make the same true for an internal site then my money is on flu finding an alternative in short order. I discussed this problem with Mingus at the time and we came to the conclusion the best option was a random subset of mAbs taken from a pool of antigenic site mAbs. This has the effect of doing to the virus what it does to us, namely providing an ever changing target to which it has to adapt.
And we do fly!