Jacob Kimmel

Yeah, yeah, yeah.

Why don't we have a million of these pills?

Okay, I'll try and take those in stride, and they're pretty different answers.

First answer is there actually are pathogens that utilize transcription factors as part of their life cycle.

So like a famous example of this is HIV.

HIV encodes a protein called TAT, and TAT actually activates NF-kappa B. And so HIV, sorry to back up a little bit, is a retrovirus.

Starts out as RNA, turns itself into DNA, shoves itself into the genome of your CD4 CT cells.

And so then it needs this ornate machinery to actually control when does it make more HIV and when does it go latent so it can hide and your immune system can't clear it out.

And this is why HIV is so pernicious is you can kill every single cell in the body that's actively making HIV with like a really good drug.

But then a few of them that have like lingered and hunkered down just turn back on.

And so people call this the latent reservoir.

Same with Hep B, right?

Well, hep B, hep C can both do this sort of like latent sort of behavior.

And so HIV is probably the most pernicious of these.

And one way it does it is this gene called TAT actually interacts with NF-kappa B. NF-kappa B is a master transcription factor within immune cells.

Typically, if I'm going to like horribly reduce what it does and some immunologists can crucify me later, it like increases the inflammatory response of most cells.

They become more likely to attack given pathogens around them on the margin.

And so it'll turn on an F-kappa B activity and then uses that to drive its own transcription and its own lifecycle.

And so I can't remember quite all the details now exactly of how it works, but part of this circuitry is what allows it to, in some subset of cells where some of that upstream transcription factor machinery in the host might be deactivated, it goes latent.

And so as long as the population of cells it's infecting always has a few that are like turning off the transcription factors upstream that drive its own transcription, then HIV is able to persist in this latent reservoir within human cells.