HTLV-1 / XMRV Conference starts today!

[WillowJ]

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?

I just want to clarify that I understand... have they ruled out accidental contamination of the cell line with pre-existing XMRV? Is that what we're asking here?

 

[WillowJ]

The Abbot Diagnostics abstract shows that a very small percentage of serology+ are cross-reactive with HLTV.

XMRV seroprevalence ranged from 0 - 0.6% in US blood
donors, HIV-1 infected and HTLV uninfected subjects.
Notably, 4.1% of Japanese HTLV-I infected individuals
were p15E reactive. Inspection of sequence homology
between HTLV and XMRV revealed a high level of conservation
within the immunodominant region of HTLV
gp21 suggesting increased seroreactivity is due to crossreactive
antibodies.

No XMRV pol
or env sequences were detected in the seroreactives.

Note the 4% is not the 4% population or 4% blood donors, but 4% of those with HTLV, so does not account for any (except perhaps a negligible) amount of Japanese blood donors testing positive for XMRV (people with cancer cannot give blood, so it could only be if they were undiagnosed at the time of donation).

 

[Bob]

I just want to clarify that I understand... have they ruled out accidental contamination of the cell line with pre-existing XMRV? Is that what we're asking here?

The Coffin paper ruled out everything for XMRV other than a recombination event happening in the specific cell line that they studied. The recombination was of two mouse viruses in the mouse that they attached the prostate cancer cell line to.

The Switzer paper totally contradicts this, and says that recombination possibilities are plentiful, and are likely to have happened in many other ways for XMRV.

This indicates that the Science editors were somewhat premature in sending the WPI the invitation to retract, and publishing their 'expression of concern' (or whatever it was), seeing as the CDC are now disputing the Coffin paper that has just been published in Science.

 

[WillowJ]

sorry, Bob, I meant to ask Alex what he meant by he said

 

[Bob]

Hi omerbasket,

I agree with your interpretations...

I'll try to answer one of your questions, based on my own understanding:

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.

Yes, Switzer is disputing Coffin's conclusions, with some interesting research.
Switzer has found many other possibilities for a recombination event to happen, that Coffin et al. didn't consider in their paper.

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):

Yes, I'm not sure either if they meant the XMRV was unlikely to created by any other recombination event from any other pre-viruses. I suppose that's quite an important thing to consider, as it makes a difference to Switzer's conclusions. But Switzer's study does seem to be quite a conclusive one.

 

[WillowJ]

In the FDA's study (woo! FDA is still interested in XMRV, too!) they looked at what type of cells XMRV infected.

Replication of XMRV could be observed in cervical and
lung epithelial cells, T-cell lines Jurkat and H9, B-cell line
HL60, U937 cells and in primary PBMC and monocytederived
macrophages. The levels of XMRV transcripts
were lower in primary monocytes compared to T-cell lines
suggesting less efficient replication in these cells.

http://www.retrovirology.com/content/pdf/1742-4690-8-s1-a225.pdf

Does this contradict Levy's study? Or not since they only infected monocytes, and did not seem to infect whole blood?

Also I see them infecting lung tissue, but not upper respiratory tissue. I did notice one of the other studies (Emory/Gupta) showing infection through mucosal tissue, but they did not include nasal passages or mouth, but did include cervix and again lung (so it helps for spousal transmission), and I'm not clear on vertical transmission. I'm also not clear on whether lung tissue clears up community transmission, which needs to be accounted for.

Emory's mucosal transmission study:
http://www.retrovirology.com/content/pdf/1742-4690-8-s1-a219.pdf

 

[Jemal]

In the FDA's study (woo! FDA is still interested in XMRV, too!) they looked at what type of cells XMRV infected.
http://www.retrovirology.com/content/pdf/1742-4690-8-s1-a225.pdf

The FDA even had two abstracts. This one is theirs as well:
http://www.retrovirology.com/content/pdf/1742-4690-8-s1-a224.pdf

The FDA is where Alter resides and I don't think they are done yet with XMRV (or MLV's).

 

[Jemal]

This abstract is also very interesting as it found XMRV in US blood donors:
http://www.retrovirology.com/content/pdf/1742-4690-8-s1-a222.pdf

It's from Abbott.

Does anyone know what this means?

Inspection of sequence homology between HTLV and XMRV revealed a high level of conservation within the immunodominant region of HTLV gp21 suggesting increased seroreactivity is due to crossreactive antibodies.

 

[leela]

I hope this conference, and the people behind all these studies, have the press clout Science and all the other negative study publishers have.
It would be great if one hundred-plus news outlets would pick up this info the way they did the retraction story for heaven's sake.

 

[Jemal]

I am guessing by the way that the people behind these papers are still standing behind them, even with the latest Science studies published. If they didn't, I am sure they would have pulled their papers, because nobody wants to look like a fool at such a conference.

 

[Bob]

Conclusion: XMRV replication was observed in GHOST cells that
express CD4, and each of the chemokine receptors ranging
from CCR1- CCR8 and Bob suggesting that infectivity
in hematopoietic cells could be mediated by use of
these receptors.
http://www.retrovirology.com/content/pdf/1742-4690-8-s1-a224.pdf

I deny everything!!! I didn't suggest anything! I wasn't even there!

 

[Jemal]

I deny everything!!! I didn't suggest anything! I wasn't even there!

You should probably sue them

 

[Bob]

You should probably sue them

hehehe... As long as they agree to give me royalties, i don't mind them quoting me!

 

[eric_s]

This abstract is also very interesting as it found XMRV in US blood donors:
http://www.retrovirology.com/content/pdf/1742-4690-8-s1-a222.pdf

It's from Abbott.

I don't know if it's smart for me to speculate about these studies, but my conclusion would be that
s l o w l y, s l o w l y they are beginning to find a little something. A part of all the truly positive cases.

I wonder who did the testing in the study by the Japanese Red Cross that is often cited and what sort of assay was used? What lab was that and did they do any further XMRV related work?

Lol, Bob, i saw this too and tried to copy and paste it, but it wasn't possible from this document.

 

[Bob]

I don't know if it's smart for me to speculate about these studies, but my conclusion would be that
s l o w l y, s l o w l y they are beginning to find a little something. A part of all the truly positive cases.

Yes, there's a whole load of scientists who are continuing with XMRV research, and it's a slow process.

It's absolutely beyond me how any scientists can say "move along now, there's nothing to see here", at such a very early stage in XMRV research.
With so many scientists agreeing that XMRV a real wild human virus, that's very difficult to detect, I can't see how XMRV can be written off so quickly.
And I don't see how anyone can say it's not in CFS patients.
If the virus exists at all in the normal population, then why would CFS patients be exempt from it?

It seems clear to me that a very few scientists can detect XMRV in tissues, but that it's even harder to detect in blood.
This seems clear from Switzer's research where he was able to detect XMRV with difficulty in some prostate cancer tissue, but was unable to detect it in the blood of any those patients. With all of the CDC's money, resources, and up-to-date PCR technologies, he was unable to detect XMRV in the blood of XMRV-positive patients, even though it's supposed to be so easy to detect XMRV with modern PCR technologies (or so we are told).
So Switzer was able to detect XMRV in tissue, but not in blood... Does this strike anyone as the way a contaminant would behave? Contamination doesn't discriminate.

And it's clearly inappropriate to declare that XMRV is simply a laboratory contamination, with all the evolving research that we are finding out about.
Already there are loads more sequences in genbank that directly conflicts with Coffin's conclusions re the recombination. And now there's Switzer's new study that also conflicts with Coffin's conclusions.

In my opinion, XMRV research is only just beginning.

Lol, Bob, i saw this too and tried to copy and paste it, but it wasn't possible from this document.

lol

 

[Jemal]

The Abott abstract was linked in the news section on the WPI website, so they must think it's important too:

http://www.wpinstitute.org/news/news_current.html

 

[eric_s]

Yes, nice find. I also think it's interesting they found around the same percentage in the US blood donors and Japanese controls. I wonder why they didn't find anything in the HIV+ Cameroonians.

 

[VillageLife]

I don't no about anyone else but after Reading that paper by abbot I can sleep well. I think helps coming!

Night xxxxx

 

[kday]

Yes, nice find. I also think it's interesting they found around the same percentage in the US blood donors and Japanese controls. I wonder why they didn't find anything in the HIV+ Cameroonians.

Because antiretrovirals probably made XMRV undetectable in their HIV patients. I don't think that's too hard to figure out.

 

[Mark]

Wowzer!

Not having time to read the abstracts myself just now, I'm especially grateful to forum members for picking out and exploring the highlights for us: thanks ever so much everyone.

Hanson's study: blinded, and detecting p-type MLVs similar to Lo/Alter. None of the XMRV-as-contamination arguments seem to apply to Lo/Alter and the PMLVs at all. Almost nobody has looked for pMLVs, they've all been focused narrowly on (disproving) XMRV. But: Hanson's study is an independent replication of Lo/Alter, no? The kind of independent replication we've been waiting and waiting for in respect of Lombardi et al (and which Lo/Alter was not accepted as). So even if we were to put the WPI and XMRV to one side and focus on pMLVs (and we will not, will we? ), then the Lo/Alter findings regarding pMLVs look very strong now - what evidence is there against them, in terms of negative papers? Almost none, I think.

And be honest: who saw Switzer and the CDC coming to the rescue?! Talk about straight out of left-field! Sounds to me like this: If it is true that XMRV sequences can be matched directly to other known MLV sequences as alternative ancestors to those Coffin identified (and this sequence-matching is easily verified) then even without any further experimentation, Coffin's theory and those ludicrously assumption-laden probability estimates are dead in the water, just days after publication!

Rumours of XMRV's demise were clearly very much exaggerated; the roller-coaster ride continues...hold onto your hats folks!