This is, quite possibly, one of the weirdest examples of convergent evolution I have ever seen.
I dont want to get ahead of myself, but HIV-1 transactivator protein (Tat) and Tomato Bushy Stunt Virus P19 are totally interchangeable. HIV and TBSV arent related, like, at all… yet two of their parts are interchangeable…
This is so weird.
Let me elaborate.
Plants dont have immune systems like you and I (dir), but they have evolved their own ways of dealing with viral infections. Because most plant viruses have RNA genomes (RNA genomes can slide from cell to cell via plasmodesmata, berry berry sneaky), a really effective antiviral for plants is RNA interference.
So RNAi is great for regulating the expression of cellular genes at the RNA level (gene regulation isnt just at the DNA level!), and for destroying RNA viruses.
Except viruses have evolved ways of interfering with RNA interference. *blink* Evolution is an arms race, man.
RNA silencing suppression (RSS) is kinda a common thing in plant viruses, considering their main adversary in plant hosts is RNA silencing machinery. One was found in influenza, and another in Ebola. But whether HIV-1 has some sort of RSS has been controversial– some labs say yes, some say no, some just look at their data and shrug.
This lab figured it out:
There are lots and lots and lots of different kinds of retroviruses. The ‘basic’ ones have three genes (gag, pol, and env) and promoters, and thats it. HIV-1 is a lentivirus– that is a ‘complex’ retrovirus that has the basic genes, plus accessories.
One of those accessories is ‘transactivator‘, Tat. If you knock out Tat in HIV-1, you dont get very many infectious particles. We figured that was because of Tats main function as a transcription factor that acts on the nascent proviral RNA (wut?!? it encourages transcription of the HIV genome, but it doesnt bind to DNA, it binds to the HIV RNA). Well this clever lab noticed that Tat also had some features in common with plant viral proteins involved with RSS. They ran some experiments and got data that freaked me out.
1– If you put HIV-1 Tat or Tomato Bushy Stunt Virus P19 in plant cells, the viral proteins interfere with RNAi.
HIV-1 Tat interferes with RNA silencing machinery in plants.
2– If you put HIV-1 Tat or TBSV P19 in animal cells, the viral proteins interfere with RNAi.
A plant virus protein has RSS activity in mammalian cells. Whoa!
3– If you mutate HIV-1 Tat in the putative RSS active sites, you dont get much viral production.
Suppressing RNAi is necessary for optimal HIV-1 production.
4– If you knock out HIV-1 Tat, and supplement with TBSV P19, you get normal HIV-1 production again.
So the decrease in particle production isnt due to Tat having some assembly functions, and that was getting knocked out. Tat has RSS activity, and if you knock it out, it can be compensated for by a plant virus RSS protein.
HIV-1 Tat and Tomato Bushy Stunt Virus P19 are totally interchangeable. Its as if this lab clipped off a birds wings, replaced it with dragonfly wings, and the bird could fly and navigate just fine.
*** As if this wasnt weird enough, RNAi doesnt work on these viruses through chopping up their RNA. The machinery just sorta snuggles up to the RNA… getting in the way, so ribosomes cant get on the RNA to make protein– Its called translational repression, but I dont know enough about how this works to blag on it… I dunno if the field even totally gets how translational repression works… A post for another day, but I wanted you all to know Im not telling you all about all the coolness in this superfriggencool paper 😛