There is some percentage of the population who have a better prognosis if infected with HIV-1 than the rest of us. Remember those pirate flags and sombreros I talk about sometimes? Major histocompatibility complexes, type I. Some people put up HIV-1 flags that are easily recognizable as ‘NOT SELF!!’ to their cytotoxic T-cells, so they (sometimes) can control the virus better, thus are slower to progress to AIDS than people with different MHC I alleles.
You notice the (sometimes) in parentheses up there.
Having a ‘protective’ MHC I allele just means that you have ~50%:50% chance of not progressing.
Why is it just 50%-50%? Why is the allele not enough for some, and enough for others?
Though the genetic diversity of humans isnt exactly huge, it could be that 50% of people with the ‘protective’ allele have one more little genetic difference that makes the allele genuinely protective, thus they do not progress, while 50% of the people with the ‘protective’ allele dont have that ‘helper’ genetic variant, thus gain no real protection from the ‘protective’ allele.
Does that make sense?
Furthermore, there could be lots of other protective alleles out there that we dont know about. Some people progress to AIDS quickly after infection, some progress slowly, why? A part of that could be the individuals genetics.
So a whole bunch of scientists did a whole bunch of work looking at a whole bunch of genetic variation in a whole bunch of HIV-1 patients (progressors and non-progressors). Whole bunch of work… to basically tell us what we have known for a really long time (MHC I alleles matter) and not much else.
I thought for sure they would find something. Hell, with a ‘Science EXPRESS!!!!!‘ paper I thought they did find something. But they didnt.
So, to sum things up, HIV-1s opinion of humans is “Theyre all pink on the inside. Pink, and CD4+ T-cells”. It doesnt particularly give a rats ass about our personal genetics.
What I found particularly disappointing about this paper, is that with literally hundreds of authors, not one of them saw the evolutionary implications of their research.
Yes, there are ‘protective’ MHC I alleles. There is not much else, on the humans genetic side, playing a role. But apparently HIV-1 can mutate away from the sequence that is harmful to it (beneficial for us controlling the virus), but this is not a ‘simple’ mutation. If the ‘answer’ to the MHC I problem were easy (1 mutation, or say 10 mutations that accumulate fitness in a stepwise manner), 100% of people with the ‘protective’ allele would progress (much like what happens with antiretroviral resistance). If it were impossible (the edge of evolution?) then 100% would be protected.
But its 50%-50%.
I think this means that HIV-1 must travel from one fitness peak to another to escape MHC I presentation and retrain functionality. Its not a simple or step-wise mutation– it needs like, 20 mutations to happen all at the same time, and its scott free. If only 11 of those 20 mutations happen, its down in a low-fitness valley (or maybe non-functional entirely). A collection of mutations that is low probability, but not impossible. Im just making up these numbers– I have no idea what the real ones are, and they are almost certainly different for every viral population in every patient. Just using them as an example. But thats the conclusion I get from this high-workload, high-PR, limited-content paper.
I think thats much more interesting than what they published. *shrug*