NIH/FDA XMRV Paper by Dr. Alter Out!

[Sean]

Thanks for that, Bob.

 

[Rrrr]

i have two remaining burning questions

1. why did alter/lo name their variants CFS1, CFS2, CFS3, and then say that there is not a direct link between these retroviruses and CFS?

2. are any of these newly discovered (alter/lo discovered) retroviruses the one Elaine DeFreitas found?

 

[Megan]

It is important to note that the HGRVs or MLV-related viruses that Alter found were not Xenotropic, because they can infect mice. ...
Instead, Alter’s MLV-related viruses are called 'polytropic', because they can infect both species (humans and mice).

There is an important point here that we need to be cautious about. If we are now talking about MLV that can infect mice, then in a prima facie sense this places a greater burden of proof onto WPI/Alter to show that their samples are not contaminated than when we were just talking about XMRV. That's because mouse contamination is frequent in labs, but when we were just talking about XMRV this was less problematic as mice are not known to be carriers of XMRV, but they do carry MLV.

I am not suggesting here that WPI or Alter have their samples contaminated, just that logically, if MLV's are involved, there is now a greater onus on positive studies to show that contamination is not an issue. I think Dr. Ruscetti recently conceded this point in the presentation referred to on the CAA website. From this perspective I don't see that the contamination accusations are going to disappear entirely until we have more positive studies. It will be interesting to see what comes out of the September XMRV conference.

Having said that, I think Dr Alter has argued strongly in is paper that contamination is not an issue. He not only ran assays designed to pick up mouse contamination but also ran his PCR reagents on over 300 negative samples and none showed up positive, which I would have thought is a good argument that the reagents themselves are not contaminated. He certainly seems very sure of himself in this regard. Aside from this, the WPI sequencing an XMRV would still seem to indicate that XMRV is an issue in at least some of us, if not most of us (in the case that we could be infected with both). The connection between the two I still find very confusing as I was unable to follow the commentary article that came out with Alter's paper.

 

[Bob]

i have two remaining burning questions

1. why did alter/lo name their variants CFS1, CFS2, CFS3, and then say that there is not a direct link between these retroviruses and CFS?

Hi Rrrr...
As far as I'm aware, Alter didn't say that there's no link... That's the whole point of this study... It is is a confirmation study that there is an 'association' between MLV-related viruses and CFS/ME. The causal link hasn't yet been proved, but unlike XMRV, these new viruses have only been found in CFS patients (the CFS patients in his study), so far, so maybe that's why he has named the gene sequences 'CFS Type 1' etc.
I'm not sure where you might have come across this piece of info, but I'm pretty sure it's incorrect.

2. are any of these newly discovered (alter/lo discovered) retroviruses the one Elaine DeFreitas found?

Good question!

 

[pictureofhealth]

RV's and RV's

Excellent stuff Bob - thank you.

How confusing that the:

RV in HGRV = retrovirus

whereas

RV in XMRV = related virus

And then we have 'MLV's' as well as 'MLV related viruses'! - which are all retroviruses (RV's)?

In addition XMRV is a MLV related virus, but an MLV related virus does not even have to be in the same part of the 'family tree' as an XMRV! It can be a P-MLV, X-MLV or even E-MLV (and one other which I've forgotten)!

Maybe 'retrovirus' could be indicated by the capitals RV, whereas
'related virus' (which is actually a retrovirus too in this instance) could have a small & large ie 'rRV'.

I bet even future top researchers are going to have trouble remembering all this!

 

[raul]

Is it possible that XMRV is associated with outbreak CFS cases and the Lo/Alter viruses with spontaneous cases?

My understanding of the 2 papers is very partial but it is as follows. I think samples from only 3 people were fully sequenced in the Science paper. The PCR test seems not to be specific for XMRV or Alter viruses. It is when you sequence the whole DNA chain that you can tell which of them it is. We know some of the Science samples were from outbreak cases. Corrections welcome.

 

[Mithriel]

Points I have taken from posters who understand the science better than I do.

The viruses found are not mouse viruses they are human viruses. XMRV has changed so much from the original mouse virus that it can no longer infect mice, but the polytropic viruses have still got that.

I read that the polytropic viruses are still 80 - 90 % similar to XMRV while some of the HIV variants are only 40%.

The Lombardi study and the Alter study have shown the results are not contamination to everyone's satisfaction except those who's careers are invested in us not having a virus. My husband works in a diagnostic lab where they run thousands of samples and contamination is not an issue, at least in the way it would have to be to get a result like these studies.

All the equipment is sterile, the samples are not open to the air, the machines are designed to not criss contaminate. They test for flu, but have never had any samples contaminated by a technician coughing over them before they realise they have flu.

If anything ever becomes contaminated it is immediately apparent. Like Alter says, every result wuld come out the same, patients and controls.

Mithriel

 

[Mithriel]

Sorry having problems posting.

They have to say that causation is not proven. It is impossible to prove causation 100% there may always be something that better techniques and more understanding could find. What will happen is a consensus will be reached, especially if antiretrovirals reduce the viral load and if patients get better with a treatment that kills the virus in vitro. There will never be proof enough for those whose careers are built on us not having a physical cause to our disease.

There are still people who insist that AIDS is not caused by HIV despite years of research and the fact that anti HIV drugs work.

The high rate of virus being found in these studies means that it must be an integral part of the disease even if it is not causative especially since it is accepted that the same family of viruses causes neurological and immune problems in animals.

ME/CFS appears to be like AIDS in that lots of bugs can get out of control or reactivated. It may be that the underlying reason this happens is still to be found but XMRV and relations must play a part.

The Elaine de Freitas virus has been well described and photographed. It is not a gamma retrovirus. Likely it is another of the things which can become part of the illness.

All this science is so new that there is going to be problems with names, they are having to be made up. There is not usually a patient group looking closely at every step and variation :Retro smile:

Mithriel

 

[RustyJ]

The viruses found are not mouse viruses they are human viruses. XMRV has changed so much from the original mouse virus that it can no longer infect mice, but the polytropic viruses have still got that.

I read that the polytropic viruses are still 80 - 90 % similar to XMRV while some of the HIV variants are only 40%.

Yes, finally a bit of commonsense. Thank you Mithriel.

 

[Daffodil]

im not sure WPI were looking for only XMRV. doesnt the ViraChip allow you to find other viruses if they are there , too?

just guessing...

 

[pine108kell]

I think the WPI was looking for other MLV viruses and only found XMRV. This is one of the somewhat disturbing results.

Regarding contamination: I am not at all familiar with the methodology of PCR and never been in such a lab. However, I will speculate. First, it sounded as though Lo/Atler really went above and beyond the usual to make sure this was not a problem. There is a second issue, which is less acceptable scientifically, but poses a strong subjective reason for not thinking contamination was a problem. Even if there was contamination, it would seem very strange that, relative to healthy controls, almost exclusively the CFS patients blood was "contaminated" in both the WPI and Lo/Alter studies. This was the case for frozen blood and blood obtained recently. What would cause CFS samples to be "contaminated" and very few controls? The odds against this seem pretty large unless someone delibrately spiked the CFS samples, which would mean unethical corruption. I doubt either in this case.

There are some strange results that still need to be clarified, and personally I am somewhat doubtful that MLVs are the cause of most CFS; however, I don't think these studies had contamination.

Even if MLVs do not cause CFS someone should try to explain WHY we have these infections and try to help us. Just saying we have compromised immune systems and that we get opportunistic infections and then once again forgetting about us totally is completely unacceptable and unethical.

 

[Bob]

Geographic area the samples were taken from:

Of the 41 patient samples, 29 were collected from 25 patients by one of us (A.L.K.) at the Chronic Fatigue Research Center, Brigham and Women's Hospital (Boston, MA). ... Most of the patients were from the New England Area.

This might be a significant reason for not finding XMRV.
I don't know if any of the WPI samples were from the New England Area.
Does anyone know?

 

[Bob]

Here's a section of the paper that attempts to explain why some studies (I don't know which studies he is referring to - but maybe it includes the CDC study) looking for XMRV might not have detected Alter's MLV-related viruses...

The 5′ gag leader sequence of previously described XMRVs represents the most divergent segment of the XMRV genome in comparison with the genomes of the other MLVs (4). In particular, there is evidently a unique 15-nt deletion in the 5′ gag leader region in all of the XMRVs previously identified in patients with prostate cancer and CFS (3, 4). To detect XMRVs in human samples with better sensitivity and specificity, some studies used a PCR primer spanning this unique deletion as the “XMRV-specific” primer (6). However, none of the viral gag gene sequences amplified from the blood samples of CFS patients and blood donors in our study has this particular deletion (Fig. S1). As a consequence, such primers might have been insensitive in detecting the MLV-related gag gene sequences that we have identified.

So he is saying that some studies have used a PCR designed to look for a specific XMRV gene sequence and would not detect the other MLV-related viruses, because of a mutation (deletion) in the XMRV strand, which doesn't occur in the other MLV-related viruses.

 

[Bob]

In this section of the paper it describes how geographic differences in different MLV-related viruses "may be considerable"... But this doesn't help explain why the WPI found XMRV in so many of their geographically diverse samples, whereas Alter found no XMRV... Except that Alter's viruses were from a small geographical area (New England area)...

Maybe the WPI will find that they had a more diverse selection of XMRVs and MLV-related viruses than they first thought...
There's so many questions, and not many answers yet.

... the heterogeneity in gag gene sequences that we observed suggests that geographic differences in different MLV-related viruses may be considerable and could affect both the sensitivity and the specificity of molecular amplification using standard primer sets.
Indeed, it is possible that the PCR primers used in various studies may have different sensitivity in detecting the diverse group of MLV-related virus gag gene sequences that we found in the clinical samples.

 

[Chris]

Hi, I am one who believes this is being a great week for all of us--not the end, but the second major step in the beginning of the end--it is great news.

In response to Rrrr's question about why Alter named those variants CFS 1 etc, I assume that as in astronomy the discoverer of a new object has the privilege of naming it. Alter states, as he has to, that causality has not yet been proven, only association; but clearly he believes that causality is almost certain, given the percentages. So he names them in such a way that all subsequent discussion will have to acknowledge at least the association, even if it tries to minimize it--embarrassing, to say the least. I think it was a very clever political move--and you don't get to be a top flight researcher without developing some political savvy--I worked in academia for 34 years.
Best, Chris

 

[Bob]

What this study means to us... (my personal take on the situation)...


Hi everyone,

It seems to me that this news has sent our world into a bit of a spin... it has mine anyway...
The results of the study weren't quite what we were expecting, and we are not quite sure what to make of it...
We were expecting an XMRV confirmation study, but there wasn't any XMRV...
We'd pinned much hope onto XMRV, and from the one study that we were expecting to validate the WPI study, there just wasn't any XMRV to be seen!

So what does this news mean for us all?

I think it is all great news for us.
Alter and co, have confirmed that ME/CFS patients are infected with a newly discovered variety of closely related Human Gamma Retroviruses.
This is big news.
No one is going to dismiss Harvey Alter's work like they did with the WPI's work.
No one is going to be able to publish any zero/zero studies now, without severe embarrassment, and they would be ignored by the scientific community if they did.

I think that whether the wider ME patient population is infected with XMRV or other MLV-related viruses, or both, is obviously a detail that needs to be resolved... but we now know that ME/CFS patients are infected with a new variety of very similar Human Gamma Retroviruses... confirmed in two studies with different patient groups from geographically diverse areas, using different diagnostic criteria.

Everything seems to fit into place.

Retroviruses are highly disruptive and an infection with a retrovirus would explain all of our symptoms.

Those patients who have so far tested negative for XMRV, might test positive for these other MLV-related viruses.

I think it is still early days in this research, and I'm sure that Alter and Mikovits will work together to better understand these new MLV-related viruses that they have both found.
I think that there is no doubt that our friend, Judy Mikovits, is working furiously on this right now.
Actually, I'm sure that she's already been working on these new MLV-related viruses for months.
Alter took his small set of samples almost entirely from the New England Area, so maybe geographical differences, and the small number of samples, explains why he did not find XMRV.

There seems to be such a lot of work going on behind the scenes that we are not allowed to know about, some of which Judy Mikovits has hinted at.
For example:
The WPI have now found different variants of XMRV;
The WPI have now done very significant research which links XMRV with immune irregularities, to be published at the end of the year;
Anti-viral drug testing trials are being planned, or have started;
And (news from Amy Dockser Marcus' Wall Street Journal blog) Judy Mikovits is now finding polytropic MLV-related viruses, like Alter's, in her original Science paper samples (i.e. she is finding both xenotropic and polytropic MLV-related viruses in individual patients).

But in the months since then, they have continued to study the CFS patients included in the Science paper and Mikovits says that almost all of them are positive for one or more MLV-related viruses, including X and P.

http://blogs.wsj.com/health/2010/08...is-mark-the-spot-in-chronic-fatigue-syndrome/

Alter seems to be supporting CFS 100%. He knows more than we do, partly because of his communications with the WPI, and he has not backed down from Human Gamma Retroviruses and their association with CFS/ME... He seems to be backing CFS all the way.

Although there's still many questions to be answered at this point in time... to me, this seems like a very optimistic time for our community and, I think, the turning point... The point of no return, in terms of scientific research.

Now we sit and watch all the funding come flooding in, all the top virologists get involved, and wait for all the ongoing studies (on HGRVs in CFS patients) to be published.

Right now, I think there's very good reason for CFS/ME patients to be hopeful.



Here's some info from the published FDA/NIH paper which I've already mentioned, but I think it's worth emphasising again, as follows:

Of the 25 CFS patients who had been rigorously evaluated at the academic medical center, 24 (96%) were positive.

So, of the patients who had been 'rigorously evaluated', to confirm that they had ME/CFS, using the diagnostic criteria that the study employed, 96% tested positive.
96% is almost identical to the final WPI figure for their cohort of 97%... It's effectively a 100% result, which I think is an astonishing result.

The other patient samples in the study were from patients who were diagnosed by their Doctors, and these patients were not rigorously evaluated for ME/CFS by the research team.

The other 12 samples from CFS patients were sent by individual clinicians taking care of patients in the mid-1990's who were given the diagnosis of CFS. We do not have details regarding the methodology by which the referring clinicians established the diagnosis of CFS.

 

[Recovery Soon]

Although there's still many questions to be answered at this point in time... to me, this seems like a very optimistic time for our community, and, I think, the turning point... The point of no return, in terms of scientific research.

I'm not sure I understand whether the CFS patients were shown to be INFECTED by these viruses, or were traces just found at this point?

I would appreciate any answers on this. Thanks.

 

[V99]

I'll say this. Finding the virus has mutated years later indicates that it must be infecting people.

 

[VillageLife]

Retroviruses have different strains......

Here is some information about HIV another retrovirus and the differences between HIV 1 and HIV 2....

HIV-2 seems to weaken the immune system more slowly than HIV-1

Those people with HIV-2 are less infectious early in the course of the disease compared to those people with HIV-1

HIV-2 seems to be more infectious later in the course of disease when compared to HIV-1

HIV-2 occurs in different parts of the world compared to HIV-1

There is no FDA licensed viral load test for HIV-2 and the viral load test used for HIV-1 is not reliable for HIV-2
HIV-2 is highly concentrated in West Africa countries such as Senegal, Nigeria, Ghana, and the Ivory Coast. HIV-2 also spreads to other parts of the world but predominantly to those countries having strong ties to West Africa; France, Portugal, and Angola to name three. Very few cases are actually reported outside of these area but on occasion do surface because of international travel.

HIV-2 is transmitted in the same way as HIV-1.

HIV-1 and HIV-2 are treated with the same medications however certain drug classes work better fighting HIV-1 than HIV-2

 

[Rrrr]

Hi, I am one who believes this is being a great week for all of us--not the end, but the second major step in the beginning of the end--it is great news.

In response to Rrrr's question about why Alter named those variants CFS 1 etc, I assume that as in astronomy the discoverer of a new object has the privilege of naming it. Alter states, as he has to, that causality has not yet been proven, only association; but clearly he believes that causality is almost certain, given the percentages. So he names them in such a way that all subsequent discussion will have to acknowledge at least the association, even if it tries to minimize it--embarrassing, to say the least. I think it was a very clever political move--and you don't get to be a top flight researcher without developing some political savvy--I worked in academia for 34 years.
Best, Chris

so this is exactly what i was thinking and wondering. i hope you are right chris.