REPOST: Frankenstein Viruses

This is a repost from the old ERV. A retrotransposed ERV :P

Its Halloween time, and we just got a BRAND NEW FRANKENSTEIN ERV! To prime you all for that post, heres a repost on an OLD FRANKENSTEIN ERV!

Remember, ERVs are junk. These are not zombie viruses. Scientists are not taking totally functional but silenced DNA or totally functional specially created by The Designer but coopted by evolution and doing stuff with it. There are ERV families-- take all the ones that are related and still have a gag or a env, figure out what their common ancestor looks like, and then do experiments with the resulting protein mashed together with a virus we know how to work with (pseudoviruses/dummy viruses). Bits and pieces of viruses smashed together to make a functional thing. Frankenstein. :-D

When they arent blubbering about 'junk DNA', science journalists predictably go all atwitter when something new or weird happens in the HIV research world. Im not impressed with pop-science HIV articles, but I do like writing posts on the science behind the articles so you all can say "Hey, I heard about that!" and talk about the real research with your friends (everyone incessantly talks about viruses with their friends... right? ... right? hehehe!)

And this is the case with a new finding that you all might have heard: Defense Against Ancient Virus Opened Door to HIV

*sigh* Okay, so get the basics from that article, forget the drama and the problems with equating PtERVs (a gamma retrovirus) becoming endogenous to HIV (a lentiretrovirus) becoming endogenous-- Lets strip the pop-science article down to the basics:

  • A component of our innate immunity against retroviruses is a protein called TRIM5a.
  • A big difference between humans and our closest relative is our lack of PtERV1 in our genome.
  • The evolution of TRIM5a in humans played a part in our resistance to PtERV1, but this same evolution has hindered our ability to fight off HIV.

Now lets flesh this out into a proper analysis of Kaiser et als experiments and findings, and why they did what they did.

When we finally got the chimpanzee and human genomes sequenced, the first thing we did was compare them to one another. A significant finding was that chimpanzees had a class of ERVs not found in humans:

"The larger family (PtERV1) is more homogeneous and has over 200 copies. Whereas older ERVs, like HERV-K, are primarily represented by solo LTRs resulting from LTR-LTR recombination, more than half of the PtERV1 copies are still full length, probably reflecting the young age of the elements. PtERV1-like elements are present in the rhesus monkey, olive baboon and African great apes but not in human, orang-utan or gibbon, suggesting separate germline invasions in these species."

So PtERV1 is a 'young' ERV family, no big whoop. Humans have their HERVs, chimpanzees have their PtERV1s, right? The strange part: exogenous PtERV1 was active when humans and chimpanzees (and gorillas) were still living in the same areas. Why the hell did they get infected with it (and not just infected-- got endogenous insertions), and we were left unscathed?

Like I said before, TRIM5a is part of the innate immune system. It binds to the capsid structure of invading retroviruses and carries them to the proteasome-- the cellular garbage disposal. Well, we already knew that TRIM5a proteins are different between primates. Chimpanzees have one kind, we have another, orangutans have another, etc. And, we already knew that our TRIM5a is a worthless 'defense' against HIV, whereas some other (not all other) primates TRIM5a can help keep HIV infection in check. So they thought a neat experiment would be to see if our TRIM5a played a part in keeping us PtERV1-free.

Minor problem: exogenous PtERVs are extinct. How can you test how well our TRIM5a works against a virus if the virus doesnt exist anymore?

Why by making a Frankenstein virus, of course!

Deniers, take note-- they did not create a zombie virus. They did not bring an ERV back to life. They took parts of an extinct virus, combined them with parts of an alive virus, and created a Frankenstein. Oh they call them 'chimeras', but you know they called it 'Frankenstein' in the lab. You know they did.

They had to make a Frankenstein monster, rather than a zombie, because the +200 PtERV1s have been mutating away from their initial sequence for a few million years. Theyre junk (OMG SHE SAID JUNK!). But, since you have +200 copies to work with, and really youre only interested in the capsid gene (the gene that interacts with TRIM5a), you can reconstruct the original PtERV capsid gene by making a consensus sequence. You can then cut/paste the capsid gene into an 'alive' virus in place of its own capsid, and voila! A PtERV1 brought back to life! Kinda!

They then tested their FrankensteinPtERV against lots of primates' TRIM5a to see if any of them inhibited FrankensteinPtERV reproduction, and lo-and-behold, humans could do it. Our gorilla, orangutan, gibbon, baboon, and African Green Monkey cousins couldnt do it.

But their TRIM5a are great at resisting systemic HIV infection.

So the researchers decided to mutated our TRIM5a to make it more like our cousins, and it lost some of its ability to restrict FrankensteinPtERV, but gained some ability to restrict HIV.

This is one of those horrible, ungodly scenarios that Creationists fear-- a mutation having a benefit in one dimension of a fitness landscape, and having a handicap in another. In this particular case, they never found a mutation that could provide resistance to both retroviruses.

But wait! Theres more!

You know how this whole thing started with researchers looking at why chimpanzees got germ-line infections with PtERVs, but humans didnt? Turns out chimpanzees TRIM5a can inhibit FrankensteinPtERV almost just as well as ours can.



So while TRIM5a plays a part in our susceptibility to viral infection, it is NOT the only factor.

Carl Zimmer at The Loom has a great article on this topic too!


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By Birger Johansson (not verified) on 27 Oct 2010 #permalink

Is Frankenstein's monster one of the undead?