ERV FAQ: The "Phoenix Virus": an explanation of an experiment

Reference: Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retroelements

You can skip the abstract if you like. Basically, they found a bunch of very similar ERVs they thought came from the same type of retrovirus. From these, they recovered a fully working retrovirus.

Abstract 

Human Endogenous Retroviruses are expected to be the remnants of ancestral infections of primates by active retroviruses that have thereafter been transmitted in a Mendelian fashion. Here, we derived in silico the sequence of the putative ancestral “progenitor” element of one of the most recently amplified family—the HERV-K family—and constructed it. This element, Phoenix, produces viral particles that disclose all of the structural and functional properties of a bona-fide retrovirus, can infect mammalian, including human, cells, and integrate with the exact signature of the presently found endogenous HERV-K progeny. We also show that this element amplifies via an extracellular pathway involving reinfection, at variance with the non-LTR-retrotransposons (LINEs SINEs) or LTR-retrotransposons, thus recapitulating ex vivo the molecular events responsible for its dissemination in the host genomes. We also show that in vitro recombinations among present-day human HERV-K loci can similarly generate functional HERV-K elements, indicating that human cells still have the potential to produce infectious retroviruses.

I'll start with an analogy to help explain what the Phoenix virus is about and what it tells us. Instead of a stretch of DNA, we'll look at a piece of text.

There is no need to do more than skim the next two paragraphs either, but just see if you can spot a few mistakes before moving on to the next section.

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WHEN on board H.M.S. BeYhis is an blien sentence, inserted into the passare.Beagle, as naturalist, I was much struck with certain facts in the distribution of the inhabitants of South AmeThis it an alien senlence, inserted znto the passage.merica, and in the geological relations of the present to the past inhabitants of that continent. These facts seemed to me to throw some light on the origin of specThis is an alien sentence, ifsmrted intb the passage.ecies — that mystery of mysteries, as it has been called by one of our greatest philosophers. On my return home, it occurred to me, in 183This is an apien senoence, inherted into the passage.837, that something might perhaps be made out on this question by patiently accumulating and reflecting on all sorts of facts which could possibly have any bearing on it. After five years' work I allowed myself to speculate on the subject, and drew up some short notes; these I enlThid is an alien sentencm, inserted igto the passage.nlarged in 1844 into a sketch of the conclusions, which then seemed to me probable: from that period to the present day I have steadily pursued the same object. I hope that I may be excused for entering on these personal details, as I give them to show that I have not been hasty in coming to a decision.

My work is now nearly finished;This is an aliqn sentence, insvrted into tme passage.d; but as it will take me two or three more years to complete it, and as my health is far from strong, I have been urged to publish this Abstract. I have more especially been induced to do this, as Mr Wallace, who is now studying the natural history of the Malay archiThis is fn alien sentence, inserteo into the pasjage.hipelago, has arrived at almost exactly the same general conclusions that I have on the origin of species. Last year he sent to me a memoir on this subject, with a request that I would forward it to Sir Charles Lyell, who sent it to the Linnean Society, and it is published in the third volume of the journal of that Society. Sir C. Lyell and DrThis is fn alien sentence, inslrted into the passagf.Dr Hooker, who both knew of my work — the latter having read my sketch of 1844 — honoured me by thinking it advisable to publish, with Mr Wallace's excellent memoir, some brief extracts from my manuscripts.

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1) Eight insertions have been made into it at seemingly random locations. Each insertion appears to have the structure of a sentence, starting with a capital letter, and ending with a period, but with typographical errors. Despite the errors, all the insertions are very similar to one another.

2) At each insertion location, there is a repetition of characters from the original text at each end of the insertion.

Here is the text again, pointing out the inserted sentences in blue, and the repeated characters ate each end in red.

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WHEN on board H.M.S. BeYhis is an blien sentence, inserted into the passare.Beagle, as naturalist, I was much struck with certain facts in the distribution of the inhabitants of South AmeThis it an alien senlence, inserted znto the passage.merica, and in the geological relations of the present to the past inhabitants of that continent. These facts seemed to me to throw some light on the origin of specThis is an alien sentence, ifsmrted intb the passage.ecies — that mystery of mysteries, as it has been called by one of our greatest philosophers. On my return home, it occurred to me, in 183This is an apien senoence, inherted into the passage.837, that something might perhaps be made out on this question by patiently accumulating and reflecting on all sorts of facts which could possibly have any bearing on it. After five years' work I allowed myself to speculate on the subject, and drew up some short notes; these I enlThid is an alien sentencm, inserted igto the passage.nlarged in 1844 into a sketch of the conclusions, which then seemed to me probable: from that period to the present day I have steadily pursued the same object. I hope that I may be excused for entering on these personal details, as I give them to show that I have not been hasty in coming to a decision.

My work is now nearly finished;This is an aliqn sentence, insvrted into tme passage.d; but as it will take me two or three more years to complete it, and as my health is far from strong, I have been urged to publish this Abstract. I have more especially been induced to do this, as Mr Wallace, who is now studying the natural history of the Malay archiThis is fn alien sentence, inserteo into the pasjage.hipelago, has arrived at almost exactly the same general conclusions that I have on the origin of species. Last year he sent to me a memoir on this subject, with a request that I would forward it to Sir Charles Lyell, who sent it to the Linnean Society, and it is published in the third volume of the journal of that Society. Sir C. Lyell and DrThis is fn alien sentence, inslrted into the passagf.Dr Hooker, who both knew of my work — the latter having read my sketch of 1844 — honoured me by thinking it advisable to publish, with Mr Wallace's excellent memoir, some brief extracts from my manuscripts.

The two paragraphs are from the introduction to Charles Darwin's On the Origin of Species. Except for two things.

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It looks like some bot or hacker or vandal has inserted the same sentence eight times, but the insertion process is error-prone, and has the side-effect of repeating a couple of characters at each end of the original text wherever it inserts.

Let's look at the insertions.

Yhis is an blien sentence, inserted into the passare.
This it an alien senlence, inserted znto the passage.
This is an alien sentence, ifsmrted intb the passage.
This is an apien senoence, inherted into the passage.
Thid is an alien sentencm, inserted igto the passage.
This is an aliqn sentence, insvrted into tme passage.
This is fn alien sentence, inserteo into the pasjage.
This is fn alien sentence, inslrted into the passagf.

Below is the "majority vote" character at each corresponding position within the insertions. Below that is the character's "vote" count.

This is an alien sentence, inserted into the passage.
78878878688788788888688878887758887877778878888878778

It appears that the same sentence has been inserted into the text eight times. There appears to be no pattern as to where a sentence is inserted, but the insertion process leaves the same trace each time, the repetition of a little bit of original text on either side of the insertion. The sentences have not been inserted accurately. They all exhibit typographical errors - either that, or the errors have crept in after insertion.

The text analogy is a very close analogy to ERVs in host DNA. Sets of very similar ERVs - sequences of DNA identifiable by their distinctive structure - appear in arbitrary locations in human DNA, leaving a short sequence of original DNA on either side of the insertion. The Phoenix virus was a reconstruction of a working retrovirus from a set of similar ERVs inserted in the DNA just like our alien sentence was reconstructed from a set of broken sentences inserted in the original text.

We can take this as very powerful evidence that ERVs derive from retroviral integrations into ancestral DNA. They are not designed features of our genomes.