The endogenous retroviruses in your genome are dead.

Dead.

Junk.

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!”

Thats not how we bring ERVs ‘back to life’usually

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:

Identification of a receptor for an extinct virus

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.

OR…

OOOOOOOOR…

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.

Comments

  1. #1 CW
    November 5, 2010

    When you say that endogination is a random event, does that include an idea that RVs were rendered innocuous by some mutation, and that mutation made them essentially naturally selected against?

  2. #2 daedalus2u
    November 5, 2010

    Correct me if I am wrong (I know you will), but I always thought that not only is endogination a random event, it is also a “one-of” event. That is it happens once, and only descendants of that single individual who had the endogination event on the germ cell that turned into the gamete that turned into them have the ERV.

  3. #3 JohnV
    November 5, 2010

    “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.”

    And then the chimpanzees started hiding silverware and ammunition in preparation for their assault on humanity.

  4. #4 The original CW
    November 5, 2010

    When you say that endogination is a random event, does that include an idea that RVs were rendered innocuous by some mutation

    The transition from exogenous retrovirus to ERV is a random event. What happens to that particular code chunk in subsequent generations could also be called random. I don’t really see how the latter might be somehow “included” in the former though.

  5. #5 Levi
    November 7, 2010

    Quick question: is it possible for the pseudoviruses you have described to recombine with lab contaminants such as MuLV’s? If that happens, would be still be talking about single round infection?

  6. #6 ERV
    November 8, 2010

    CW– The mutations were almost certainly selected for, as mutations that render the ERV non-functional provided a back-up for epigenetic control. The precise mutations are random (no reason why an independently inserted ERV in say, humans and chimps, would have the exact same mutation/deletion/frame-shift), other than common descent, not independent insertions.

    daedalus2u– Yup! We are all related. Really related :-/

    Levi– Packaging of the genome is key. Lets say this artificial Env ‘stole’ a contaminant MLVs structural proteins. It would still package the MLVs genome, with the non-novel Env. Thus you would still just get MLV out in the end. I might make a post specifically on pseudoviruses with colors and stuff to really explain how cool and safe this is :)

  7. #7 Katharine
    November 12, 2010

    Possibly an obvious question, but are there genes in any genome we’ve sequenced that originate from ERVs?

  8. #8 W. Kevin Vicklund
    November 13, 2010

    The example that immediately comes to mind is that some ERV LTRs act as promoters for placental genes. I am not aware of any exons that contain ERV fragment, though I am only a layperson.

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