The endogenous retroviruses in your genome are dead.
They no longer code for functional, infectious viruses.
Those viruses are also extinct. They were floating around thousands, millions of years ago, infecting stuff, and now they are hanging out in your genome instead (100% of humans are infected, *wink*).
ERVs are viruses that we have, functionally, tamed. We have overcome them.
Thus, it would be useful to ‘bring ERVs back to life’ so we can study them and figure out how we conquered them, hopefully giving us idea how to treat modern day infections.
“OMFG!” a crazy person might say. “UR BRINGIN ERVS BAK TO LIVE! EPIDEMICS KILL BAZILLIONS NO MAH GAWD!”
Lets say you have 100,000 ‘ERV’ genes/LTRs/etc. Lets say there is a family of ERVs that has 100 members– some are a gag and a pol, some are just an env, some are just LTRs, etc. Lets say there are 8 kinda sorta ‘complete’ env genes from the same family. Each one of them has been inactivated in a different way (one has a frame-shift, one has a different frame shift, one has a deletion, one has a stop codon, etc). You can put all of those kinda-sorta envs together and figure out what their functional ancestor might have looked like! We can then make an ‘envelope expression vector’– a bit of DNA that when you give it to a mammalian cell, the cell will make the envelope protein. Not every other part of a retrovirus, only the envelope protein.
You can then give the cells another bit of DNA, say one that codes for every protein MLV needs except the envelope gene.
Only envelope + Everything but envelope = Functional virus you can use in experiments to characterize the envelope!
These are called ‘pseudoviruses’ because the functional virus will package the ‘everything but env’ genome, so while it can infect cells, it cant get out again. Single-round infection. Super safe way to study these viruses.
This is precisely what they did in this paper:
They ‘resurrected’ a chimpanzee ERV env, because its only found in chimpanzees, not humans. By bringing this guy back to life, scientists were hoping to figure out why chimpanzees were infected, but humans werent.
Turns out, this chimpanzee ERVs envelope protein can infect humans just fine. Nothing like our receptor doesnt look like chimpanzees receptor anymore, or our receptor gene is now a pseudogene or something. This ERV env likes human cells just fine!
The authors proposed several ideas of why this virus was endogenized in chimpanzees but not humans:
… human ancestors were ecologically isolated from viral reservoirs during the time of its exogenous replication, or that endogenous proviruses were lost during passage through genetic bottlenecks. It is also conceivable that behavioral changes in nascent humanity limited acquisition or dissemination of these viruses. The possibility also remains that human ancestors were protected from these γ-retroviruses by cytidine deaminases (6), other unknown restriction factors, or effectively suppressive adaptive immune responses.
Which led to other scientists to talk about and appreciating chance, which I like:
“Chance could have played a big role in this,” agrees Bieniasz. “It could be that human ancestors were ecologically isolated from the primate species in which these viruses were replicating.” Behaviour offers another explanation. “It might be that we didn’t bite each other or didn’t indulge in some behaviour that facilitates transmission of these viruses,” he adds.
Humans were infected, numerous times and places, but it never endogenized in humans. Endogenization is a random event. Humans are exposed to zoonotic viruses and retroviruses more frequently than you might think– Humans lacking this particular CERV does not mean humans were never infected with this CERV. It only means that the exogenous version of this CERV never became an ERV in humans.
Sometimes, shit just happens. And you get screwed.
Sometimes, shit just happens. And you actually catch a break.
And sometimes, shit just happens.