HIV-1 usually evolves around this to ‘hide’ from CTLs. Maybe it puts a sombrero on the skull so the CTLs think its a party boat. But while HIV-1 evolves ways to hide from cytotoxic T-cells, this escape comes at a fitness cost. So if the sombrero-pirate-flag-HIV is transmitted to someone with a different MHC type whos CTLs couldnt see that pirate flag in the first place, HIV-1 is going to take off the sombrero and regain fitness.
The Problem: HIV-1 is figuring out how to evade CTLs… while maintaining fitness.
HIV-1 is never taking the sombrero off. Even if it is being transmitted to someone who does not put up a pirate flag with a skull, the sombrero isnt going away. So then if the person who puts up a flag without a skull on it transmits to someone who does put up a flag with a skull, the sombrero is still there, and HIV-1 can escape their CTL response with absolutely zero effort. How?
A paper was just published in PLOS Pathogens, where they made a mathematical model that explains what is going on. Basically, escape from CTL responses, on a global scale, can be measured in years. Reversion of those escape mutations can be measured in decades.
Yes, we can find and describe individual transmission pairs, where one persons HIV-1 puts on the sombrero hat, and then gets transmitted to someone else who doesnt present a skull, and the sombrero goes away. Environmental pressure–> Selection of escape variant–> Relief of environmental pressure–> Reversion. Dir. But when we look at the population, world-wide scale, HIV-1 is learning how to pick our locks. All of our locks. At the same time. Its escaping our immune responses much faster than it ‘forgets’ and reverts.
If we are going to make an HIV-1 vaccine to stimulate the CTL branch of our immune system, we need to do it NOW, or it is never going to happen. HIV-1 will figure out how to be invisible to an entire branch of our immune system. All of us.
This doesnt just suck for vaccines, either. Slower disease progression is associated with a strong initial CTL response. If youre infected with a variant that, from Day 1, can escape your CTLs…