HTLV-1 / XMRV Conference starts today!

[currer]

Exciting, isnt it?.....I'm going to have a rest, now.

Well, these abstracts have made me feel more optimistic than I have done for months, or even a year!

I'm amazed that there's so much positive research here!

Hanson's study looks far more solid than I thought it would be. It is blinded, and she has used IAP to check for contamination etc. It's interesting that she has detected p-type MLV's.

Switzer really seems to be on our side. He genuinely seems to be interested in XMRV. This is very positive news. This abstract challenges Coffin's latest study published in Science. So the CDC are challenging Coffin's recombination paper that prompted the Science editors to write the letter to the WPI. Wow!!!

 

[Bob]

Is this recombination generally, or recombinations that formed XMRV?

It's a big difference. There's a lottery draw every week... but it would be really unlikely to get the same numbers every week. I just listened to the virology podcast, and they said that the chances of two recombinations both forming XMRV would be a hundred million times less likely than your lottery ticket coming up.

I don't understand the data/mechanics enough to have my own opinion, but that's what they said.

It looks like Switzer is challenging Coffin's opinion that this specific recombination event can only be one in a trillion.
I think he is saying that it is far more likely.
This is based on looking at a number of MLV genomes, taken from genbank, and seeing if they could recombine into a short XMRV sequence.
He says that it is very likely, and that's only based on a small sample of MLV genomes that he studied.
It blows Coffin's conclusions out of the water!

 

[Bob]

Exciting, isnt it?.....I'm going to have a rest, now.

Yes, my head is hurting too!!!

 

[Bob]

I think that these papers are revealing how readily MLVs recombine. Deckoff-jones once said that it was not convincing to argue that recombination would be a one-off event.
I suppose it is possible that MLVs have been infecting the human population for some time. XMRV may just be the latest and more adapted virus to come along. As viruses travel into new environments (humans) they will re-adapt to be more successful. XMRV could be just the latest one. Coffin could be right, but it proves nothing about MLVs as a potential pathogen in ME/CFS.

Yes, I totally agree with you there currer.

 

[Enid]

Thanks all for the information - looking very exciting.

 

[Jemal]

At the IiME conference, I believe that Beiger said that he was trying to improve his results, by refining his methodology and assays, etc.
He currently has a 40% detection rate, and wanted to improve his study.
So maybe that's why he's withdrawn his abstract?

Bieger is a different study? So I don't understand your reply

 

[Bob]

Bieger is a different study? So I don't understand your reply

Ah, yes, sorry!!!

I'm easily confused!!!



Please ignore that post... I'll go back and delete it!

Hope i didn't confuse you too much Jemal! (Well spotted by the way!)



(I don't have any idea why De Meirlier might have withdrawn his paper.)

 

[Jemal]

DeMeirleir should be speaking on the symposium "XMRV, a recently discovered human retrovirus: What do we know about it?" being held on 9 june.
Patients are also going, so we should get some reports.

 

[alex3619]

Contamination revisited.

I am still thinking about recombination arguments. There are several points.

Let me state again, before I begin, that Coffin's result could have been from contamination from infected lab workers or mice. Were they tested? Some others are also asking this question, but I leave it to them to speak.

The argument that recombination derived XMRV is highly improbable is based on flawed probability calculations. I wish an expert on probability would get with a retrovirologist, and really look at this. It is unlikely that recombination is totally random. Highly unlikely, although I could be wrong. That alone makes the math suspect. So the real probability is not likely to be so remote. In addition, once you factor in all the species, all the MLVs, and all the recombinations, XMRV might have arisen in many different vectors. A particular strain of mouse using in prostate cancer culture creation is only one candidate.

It is highly improbable that the cell line in discussion is the only place it could have happened. Therefore, purely on the basis of probability, but presuming other MLV recombinations could give rise to XMRV, it is highly improbable that it arose in the cell line. The argument rests on XMRV suddenly appearing in the cell line. I ask again: have they ruled out contamination?

Please do not misunderstand the power of evolution. I spent some time studying the math behind genetic algorithms. Simple mutation is a minor and not very powerful mechanism for change. The real power in evolution is recombination.

The following calculation is only indicative, based on rough guesstimates, which make it highly unscientific. I am just trying to get a sense of things. I would like to see it done by someone with real expertise in this area.

Lets look at the total mammalian population in the world. It has to be many many billions - maybe hundreds of billions (many trillions?). If only 0.1% are infected with MLVs, then the total number infected is hundreds of millions. But wait, these individuals have numerous viral replications, in probably millions of cells. Lets be a little conservative, although the exact number is not very relevant. Lets say there are only a billion in the life of an individual. That is maybe one hundred million billion potential recombination events. Let me be sure we are on the same page, I mean 100,000,000,000,000,000 events. This could have happened over a century - call it ten generations, although this is also conservative. So we have ten to the eighteen possibilities. What are the odds that XMRV did not arise in one of them? Given that it might not be entirely random, and so simple probability math may not be valid?

It is worse than this. This ignores the multiple sequences of recombination events. It is much more likely, based on my admittedly limited understanding which could be wrong, that XMRV arose several times.

The only way to argue against this is to say that recombination events are rare - and that does not seem likely. Once it arose, it can spread and further mutate. How many mammalian species have been tested for XMRV infection? Does this include cats, dogs, cattle, sheep, bats and wild rats? How about all the other mammals?

There are still huge questions about XMRV and MLVs in humans. All I am saying is that contamination by a lab derived XMRV strain is not the only possibility. Please note that any of the numbers I used in my calculation could be wrong - please feel free to substitute your own.

The abstract by Prosperi, Switzer et. al. indicates that recombination is common, and it could result in XMRV.

I hope the Hanson study is a precursor to the BWG and Lipkin, although I also dread it being right. I don't want a "new" retrovirus rampaging through the world populations - but if one is the sooner we find out the better. Bring on the research!

The pressing question question to me is how did Erlwein et. al. get contamination but not in controls? Does anyone know the details? They claim to have something to say about the source of contamination. Depending on what it is, it could be important.

Bye
Alex

 

[Jemal]

Thanks Alex, a lot of text, but I could follow it easily. I am with you here that recombination events might not be that rare.
Mammals also have a low life expectancy and they breed a lot, creating a lot of oppertunity for a recombination event I think. Also they are everywhere where humans are.

 

[Bob]

Hi Jemal,
Would you mind doing me a big favour please?
Could you add the latest abstracts from your recent post (link) to your original list of abstracts (link) please?
This is so I can create a link to your post, with all the info in it, as a handy reference.
Hope that's not too much bother?

Or if you unable to do it, then I can copy and paste the info into a new post.

Thank you,
Bob

 

[Jemal]

Hi Jemal,
Would you mind doing me a big favour please?
Could you add the latest abstracts from your recent post (link) to your original list of abstracts (link) please?
This is so I can create a link to your post, with all the info in it, as a handy reference.
Hope that's not too much bother?

Or if you unable to do it, then I can copy and paste the info into a new post.

Thank you,
Bob

It's done Bob, I edited my original post.
I am hoping for more abstracts by the way, the last 4 were just articles and not PDF downloads.

 

[Bob]

It's done Bob, I edited my original post.
I am hoping for more abstracts by the way, the last 4 were just articles and not PDF downloads.

Thanks very much Jemal. Much appreciated.

 

[eric_s]

The pressing question question to me is how did Erlwein et. al. get contamination but not in controls? Does anyone know the details? They claim to have something to say about the source of contamination. Depending on what it is, it could be important.

Bye
Alex

I agree this will be interesting. But what sort of controls were these? It sounded a bit like it was not samples of the same kind as the cases.

 

[Bob]

The pressing question question to me is how did Erlwein et. al. get contamination but not in controls? Does anyone know the details? They claim to have something to say about the source of contamination. Depending on what it is, it could be important.

Bye
Alex

I saw McClure's name associated with that paper, and decided not to pay too much attention to it!

 

[Jemal]

I saw McClure's name associated with that paper, and decided not to pay too much attention to it!

LOL

(had to post a few more words, because otherwise the message was too short)

 

[Bob]

Regarding the theory of recombination in a prostate cancer cell line, I read a new possible theoretical scenario recently.
It might be the case that the XMRV in the prostate cancer cell line actually originated in the human prostate cancer sample, and not in the mouse/mice.
But Coffin et al. were unable to detect the XMRV in the original prostate cancer sample, or the earliest cell line, due to low copy numbers.
It might be the case that the cell line is a perfect breeding place for XMRV to replicate, and so after the cell line had been propagated for a while, XMRV copy numbers increased, which enabled detection.
So their whole paper might be based on a false theory, due to inadequate detection techniques.

I can't remember where I read this... If I find the quote, I'll add it to this post.

 

[WillowJ]

Read this and see if you still have doubts about XMRV:

Development of XMRV producing B Cell lines from lymphomas from patients with Chronic Fatigue Syndrome
Francis Ruscetti, Vincent C Lombardi, Michael Snyderman, Dan Bertolette, Kathryn S Jones, Judy A Mikovits.
http://www.retrovirology.com/content/pdf/1742-4690-8-s1-a230.pdf


And here's more evidence that XMRV is a human virus:

Restricted infection of xenotropic murine leukemia virus-related virus in human lymphoid tissue
Marta Curriu, Jorge Carrillo, Marta Massanella, Elisabet Garcia, Bonaventura Clotet, Julian Blanco, Cecilia Cabrera.
http://www.retrovirology.com/content/pdf/1742-4690-8-s1-a208.pdf

nice, thanks

 

[WillowJ]

The argument that recombination derived XMRV is highly improbable is based on flawed probability calculations. I wish an expert on probability would get with a retrovirologist, and really look at this. It is unlikely that recombination is totally random. Highly unlikely, although I could be wrong.

That's true that it's highly unlikely that recombination is random, but this is genetics, not probability. Shouldn't Coffin know this?

 

[omerbasket]

I think that the following study seems like a very important one:
http://www.retrovirology.com/content/8/S1/A235
I have to say that I find it very hard to understand some of the things written there, but I'll try to do it anyway and please correct me if I'm wrong. Coffin's paper says the following:

We conclude that XMRV was not present in the original CWR22 tumor but was generated by recombination of two proviruses during tumor passaging in mice. The probability that an identical recombinant was generated independently is negligible (~1012);

His probability calculations seem arbitrary to me, prboably not taking into consideration the charachetristics of MLVs.

Anyway, look at the things that the paper written by Prosperi, Switzer et al. says:
First of all, I'll continue a little bit with Coffin's paper. It says:

Phylogenetic analysis indicates that
PreXMRV-1 groups with xenotropic viruses whereas
PreXMRV-2 appears to be a recombinant, grouping with
polytropic and modified polytropic viruses for certain
stretches of its genome (fig. S5).

But Switzer's abstract says:

Eight eco/poly/xenotropic MulV complete genomes were selected from GenBank, plus an XMRV sequence. The dataset showed strong phylogenetic signal. By tropism-group analysis using SimPlot software, XMRV was detected as a mosaic recombinant form of all three groups.

So, if XMRV is a recombinant of ecotropic MLVs with the two other types - why does Coffin's Pre-XMRV1 and Pre-XMRV2 are just xenotropic or polytropic/modified polytropic? By the way, that's still a question, so again - I'm open to hear why I might be wrong.

Secondly, as I quoted above, Coffin says that the probability that an identical recombinant was generated independently is almost impossible. I don't know if he mean and identical recombinant meaning that his "pre-XMRV1" and "pre-XMRV2" would have met each other somewhere else, or that he means that another even would create XMRV, but in both cases, it seems to me the the following sentences seems to go directly against his argument (that it must be that XMRV was created without human intention only once, and it was with the pre-22Rv1 cell lines):

Given the evidence of inter-tropic recombination in MuLV, detection and classification of recombination in XMRV using different MuLV tropism prototypes should be interpreted with caution [...] These results suggest that identification of parental strains of the potential recombinants is difficult and that recombination in the highly genetically related MuLV have been occurring for some time.