Paolucci et al: 2 out of 12 CFS patients positive for MuLV

[Bob]

Anyone care to explain or help me understand/interpret the highlighted parts below from the full paper please?

'It is however intriguing that the only positive results were obtained in these patients. On the other hand, in both cases the positivity could not be confirmed by the amplification of a different virus gene.

That just means that they could only detect a single gene in each of the two patients. (one was the gag gene and the other was the integrase gene.)

The proviral DNA amount was very low in our patients,

That just means that the copy numbers of the viruses were very low.

which might explain the stochastic amplification of a single virus gene in each of the two positive patients.

That means that the detection of sequences was random, or unreliable, in that they could only detect a single gene in each sample. If the virus was present, then it might be expected that more genes could be detected, but if copy numbers are at the limits of detection, then maybe it's not so surprising.

Another possibility is that only fragment of virus DNA might be present in biologic samples.

This suggests that a whole virus is not present in the samples, but just a fragment of viral DNA.

In conclusion, while it appears established that XMRV/MLV sequences are not detectable in a significant proportion of CFS patients, the frequency and the role of evolutionary relic retrovirus sequences potentially detectable in the human chromatin remain to be further elucidated.'

I originally thought that 'evolutionary relic retrovirus sequence' is a reference to human endogenous retroviruses (HERVs), but now I think they are talking about any endogenous retroviruses, including mouse ERVs.

(If they are only talking about HERVs, then the paragraph doesn't seem to make much sense, as they just start talking about HERVs out of nowhere.)

If they are talking about all endogenous retroviruses, then they just mean that more research is needed before any conclusions can be made in this field of research. They are raising a question about the nature of the sequences, and where they originate from.


Edit: I've completely changed the last section of my text.

 

[JT1024]

I've read it now, and the results don't seem very impressive.

Firstly, the fact that no controls contained any sequences, is the first indicator that controls and patient samples could have been handled differently. I would expect that at least one of the controls might show up as positive, if the positive results were not based on contamination. (But this would not necessarily be the case, considering the low numbers involved.)

Secondly, the sequences that they detected are not helpful, as per my current understanding. The first sequence, 'CFS Pavia-1', was similar to Lo's sequences, but not the same, but it was 100% identical to a polytropic mouse virus.
And the second sequence, 'CFS Pavia-2', was 100% the same as XMRV VP-62.

The fact that the sequences were 100% identical to XMRV VP-62 and an ERV is not helpful, with regards to proving it is a human virus. It suggests that it could be contamination.

That's my understanding so far, but I might have misunderstood something.

Regarding your concerns Bob,

Firstly, if anyone performing research is handling patient samples and controls differently, the study should be tossed. This is basic lab science 101. The whole purpose of a "control" is to validate that the assay is working as it is designed. If controls do not work, the assay is in question. If a "scientist" isn't questioning the assay, they need to get their butt off the bench and back into remedial education. No one with a grant should have anyone working for them without this basic understanding.

While the first sequence was similar to Lo's sequences, I am not surprised at all that there is a variance. To date, I don't believe anyone has elucidated how these MLV-like sequences have been introduced into humans. That is the million dollar question. To have "XMRV" or VP62 raises the question of contamination again. I admit, I have little time to study these papers as I would like. The publication provided very limited information IMHO.

Given my limited time and often diminished mental capacity, my thoughts are along the lines that we all have a percentage of our genome attributed to HERVs. Most of us also have been given vaccines (developed utilizing various mammalian substrates) where previously unknown adventitious agents could recombine with HERV's to become newly formed, possibly pathogenic viruses. Evidence I've recently encountered indicates the US government (FDA/NIH), big pharma, and academia are well aware of the threat. (google MIT Consortium Adventitious Agent and see what you find. I have a great powerpoint presentation that outlines the whole issue - and this is very current news!) If you have trouble finding it, I do have the documentation.

In addition to vaccines as a source of adventitious viruses, our normal exposure to many viruses potentially provides the opportunity for these viruses to recombine or reactivate latent viruses or HERVs.

What more can I say? There is an abundance of information. It is every individual's choice what they believe - that is unless they are not provided the necessary information to make that choice.

 

[Bob]

Firstly, if anyone performing research is handling patient samples and controls differently, the study should be tossed. This is basic lab science 101. The whole purpose of a "control" is to validate that the assay is working as it is designed. If controls do not work, the assay is in question. If a "scientist" isn't questioning the assay, they need to get their butt off the bench and back into remedial education. No one with a grant should have anyone working for them without this basic understanding.

I was talking about the control subject samples, rather than the negative or positive PCR controls. I have altered my previous post to make that clearer.

While the first sequence was similar to Lo's sequences, I am not surprised at all that there is a variance. To date, I don't believe anyone has elucidated how these MLV-like sequences have been introduced into humans. That is the million dollar question. To have "XMRV" or VP62 raises the question of contamination again. I admit, I have little time to study these papers as I would like. The publication provided very limited information IMHO.

I think the more significant point is that the gag sequence is 100% identical to a polytropic mouse virus.

Given my limited time and often diminished mental capacity, my thoughts are along the lines that we all have a percentage of our genome attributed to HERVs. Most of us also have been given vaccines (developed utilizing various mammalian substrates) where previously unknown adventitious agents could recombine with HERV's to become newly formed, possibly pathogenic viruses. Evidence I've recently encountered indicates the US government (FDA/NIH), big pharma, and academia are well aware of the threat. (google MIT Consortium Adventitious Agent and see what you find. I have a great powerpoint presentation that outlines the whole issue - and this is very current news!) If you have trouble finding it, I do have the documentation.

In addition to vaccines as a source of adventitious viruses, our normal exposure to many viruses potentially provides the opportunity for these viruses to recombine or reactivate latent viruses or HERVs.

I'm very interested in HERVs, and the possibility that reactivation or recombination of HERVs might lead to diseases.

What more can I say? There is an abundance of information. It is every individual's choice what they believe - that is unless they are not provided the necessary information to make that choice.

I'm not sure if that comment was directed at me, or not, but I was purely commenting on the strengths/weaknesses of this specific study.

 

[JT1024]

[quote="Bob, post: 284557, member: 558"
I'm not sure if that comment was directed at me, or not, but I was purely commenting on the strengths/weaknesses of this specific study.[/quote]

Bob, it was not directed at you or anyone in particular. Those capable of understanding know the implications.

On the other hand, it is my belief that viruses or proviruses, whether naturally occurring or introduced via lab produced vaccines, biologics, vectors, etc have the ability to recombine to produce new, "hybrid" viruses previously unknown. The ability to detect these types of recombinants has been challenging (as previously mentioned re MIT Consortium of Adventitious Agents)

While these new viruses may not kill you as quickly as Ebola or SARS, they may have already demonstrated the ability to "neutralize" previously healthy, highly functional, highly intelligent, and motivated people who previously contributed substantially to the GDP in the US and were not "slackers" .

Perhaps I've read too many medical thriller novels .. or perhaps I've worked in healthcare too long. I think anyone in any industry can say, "The more you know, the more you don't want to know". Ignorance truly can hurt you.

 

[Bob]

To clarify my earlier post, I think that the paper says that the gag gene that they detected (CFS Pavia-1) is 100% identical with the gag gene of the polytropic mouse virus, genbank accession number FJ544578, which was detected in this paper:
http://jvi.asm.org/content/83/6/242...&searchid=1&FIRSTINDEX=270&resourcetype=HWFIG

 

[barbc56]

I've read it now, and the results don't seem very impressive.

I've finally had a chance to read the whole study and taken a look at what other scientist/blogs are saying and it looks like there could be some possible problems.

1.This study was done in 2010. It's important to look at this study in the context of when it was written. At that time we did not have the same information we have today.

2. The two MLVs/genes were different plus the viral load was so low that it would most likely not cause symptoms, let alone illness. If this was a causative factor they would have found MLVs/genes in more than two patient samples

It is however intriguing that the only positive results were obtained in these patients. On the other hand, in both cases the positivity could not be confirmed by the amplification of a different virus gene. The proviral DNA amount was very low in our patients, which might explain the stochastic amplification of a single virus gene in each of the two positive patients. Another possibility is that only fragment of virus DNA might be present in biologic samples.

Stochastic means involving chance or probability. It could be a completely random event that they even found the two virus genes.

In conclusion, while it appears established that XMRV/MLV sequences are not detectable in a significant proportion of CFS patients, the frequency and the role of evolutionary relic retrovirus sequences potentially detectable in the human chromatin remain to be further elucidate

This study was done in 2010, and at that time further study was indeed needed. This did happen and subsequent studies were negative. It could also be that this was more of a pilot study that might have led to further research but when more negative studies started coming in it was not examined further.
Barb C.:>)

ETA. I was responding to Bob's post on the bottom of page 2. I didn't realize there was a page 3. Apologies If I have repeated information.

 

[currer]

In her Invest in ME talk last year, Dr Mikovits talks about finding a range of polytropic MLVs in her samples and mentions that fragments of virus can also be pathogenic. I will listen again and post anything relevant to this discussion. There is quite a bit of info in that talk - its a year old - it ought to be OK copyright wise to quote a bit.
But I cant do it right away. Im too busy just now!
It is an interesting talk in that it reflects what she was doing just before everything went wrong for her and she was silenced. Most of what she says never got near publication.

 

[RustyJ]

The two MLVs/genes were different plus the viral load was so low that it would most likely not cause symptoms, let alone illness. If this was a causative factor they would have found MLVs/genes in more than two patient samples

Hi Barb, I'd be interested to hear what level of MLVs in plasma you consider would cause symptoms, and how you relate that to issues of latency and neuro-inflammation (which is probably due to tissue damage and quite separate from viral load at any one moment) .

 

[barbc56]

In her Invest in ME talk last year, Dr Mikovits talks about finding a range of polytropic MLVs in her samples and mentions that fragments of virus can also be pathogenic. I will listen again and post anything relevant to this discussion. There is quite a bit of info in that talk - its a year old - it ought to be OK copyright wise to quote a bit.
But I cant do it right away. Im too busy just now!
It is an interesting talk in that it reflects what she was doing just before everything went wrong for her and she was silenced. Most of what she says never got near publication.

Pathogenic means it causes disease and these particular MLVs have not been shown to cause disease, specifically me/cfs. Do you mean infectious? XMRV is infectious but benign.

Barb C.:>)

 

[lansbergen]

XMRV is infectious but benign.

Like ME is benign?

 

[currer]

Pathogenic means it causes disease and these MLVs have not been shown to cause disease, specifically me/cfs. Do you mean infectious? XMRV is infectious but benign.

Barb C.:>)

Barb, You cannot be serious. We have just been discussing this.

"In summary, our results indicate that the transforming capacity of 22Rv1 cells is strongly dependent on the presence of XMRV."
http://forums.phoenixrising.me/inde...kine-expression-and-tumor-angiogenesis.18669/

 

[Firestormm]

Cheers Bob, Barb, (even) JT

 

[Bob]

barb, I don't agree with your interpretations.

...it looks like there could be some possible problems...

The two MLVs/genes were different

Yes, the two genes that were found were not from a known single source.
But as MLV recombinations are so common, and many of the other MLVs detected in other studies are from unknown sources, this doesn't really tell us much. The two sequences could potentially be from a single unknown source.

plus the viral load was so low that it would most likely not cause symptoms, let alone illness.

I'm not aware of any evidence that demonstrates what viral load of XMRV infection in humans is necessary to cause symptoms.
What level of retroviral sequences in the blood is safe and acceptable?
What level of novel retroviral sequences in the blood would you expect to be symptom-free?
We've repeatedly discussed the possible reasons and implications for low copy numbers in the blood, so this is not a new issue.

If this was a causative factor they would have found MLVs/genes in more than two patient samples

Considering everything that we've discussed in the past, Barb, this is a very questionable statement. Amongst other issues, there are issues of latent viruses, problems with PCR detection, limits of PCR detection, and viral reservoirs.

Stochastic means involving chance or probability. It could be a completely random event that they even found the two virus genes.

No, it doesn't mean a random event, as if the sequences dropped out of the sky.
It means that the results are unreliable, and that there was no consistency or predictability of finding genes.

I think that this is a weak and pretty meaningless study, but not for any of the reasons you have given.

XMRV is infectious but benign.

And how many humans have been intentionally infected with XMRV to test this hypothesis?

 

[natasa778]

While the first sequence was similar to Lo's sequences, I am not surprised at all that there is a variance. To date, I don't believe anyone has elucidated how these MLV-like sequences have been introduced into humans. That is the million dollar question. To have "XMRV" or VP62 raises the question of contamination again. I admit, I have little time to study these papers as I would like. The publication provided very limited information IMHO.

Given my limited time and often diminished mental capacity, my thoughts are along the lines that we all have a percentage of our genome attributed to HERVs. Most of us also have been given vaccines (developed utilizing various mammalian substrates) where previously unknown adventitious agents could recombine with HERV's to become newly formed, possibly pathogenic viruses. Evidence I've recently encountered indicates the US government (FDA/NIH), big pharma, and academia are well aware of the threat. (google MIT Consortium Adventitious Agent and see what you find. I have a great powerpoint presentation that outlines the whole issue - and this is very current news!) If you have trouble finding it, I do have the documentation.

In addition to vaccines as a source of adventitious viruses, our normal exposure to many viruses potentially provides the opportunity for these viruses to recombine or reactivate latent viruses or HERVs.

What more can I say? There is an abundance of information. It is every individual's choice what they believe - that is unless they are not provided the necessary information to make that choice.

Consequences of realisation that something like this has happened, or is happening, would be breathtaking. In more than one way. IMO the need to shake away the possibilty that infectious pathogenic retroviruses have been introduced on a large scale via biologicals, not to mention the sacred cow of vaccines, is pervasive amongst virologists, yet largely unspoken. It is the driving force behind muddy hypothesis such as paprothka-coffin one being cemented and turnining into myths overnight. Fear creates religion and myths. At the moment we have the Myth of Immaculate Recombination and the Myth of Immaculate Contamination. The Myth of Immaculate Harmlessness is being born as we speak. The Harmless Retrovirus Myth. If that one doesn´t stick then the myth of Something-Something-Host-Genes-Something-Are-To-Blame will be born very soon. We will be hearing how is not the fault of the virus but of faulty host genes that are too permissive to pathogen LOL. Mark my words!

The anxiety amongst science bloggers is palpable. Many of them have recruited most of their faitful followers by guarding myths and ridiculing and excommunicating unbelievers. If the biggest myth of all was to crumble they would have very rough time indeed. But on the larger scale of things that would be the last of humanity's woes.

 

[natasa778]

barbc56 said: ↑

plus the viral load was so low that it would most likely not cause symptoms, let alone illness.​

​

​

Let me guess, this is coming from the science bloggers (aka Defenenders of the Holy Fortress). WOW, we are witnessing the Myth of Harmless Retrovirus as it is being born. History in the making

 

[Firestormm]

Consequences of realisation that something like this has happened, or is happening, would be breathtaking. In more than one way. IMO the need to shake away the possibilty that infectious pathogenic retroviruses have been introduced on a large scale via biologicals, not to mention the sacred cow of vaccines, is pervasive amongst virologists, yet largely unspoken. It is the driving force behind muddy hypothesis such as paprothka-coffin one being cemented and turnining into myths overnight. Fear creates religion and myths. At the moment we have the Myth of Immaculate Recombination and the Myth of Immaculate Contamination. The Myth of Immaculate Harmlessness is being born as we speak. The Harmless Retrovirus Myth. If that one doesn´t stick then the myth of Something-Something-Host-Genes-Something-Are-To-Blame will be born very soon. We will be hearing how is not the fault of the virus but of faulty host genes that are too permissive to pathogen LOL. Mark my words!

The anxiety amongst science bloggers is palpable. Many of them have recruited most of their faitful followers by guarding myths and ridiculing and excommunicating unbelievers. If the biggest myth of all was to crumble they would have very rough time indeed. But on the larger scale of things that would be the last of humanity's woes.

I won't claim to understand much of what you are saying Natasa let alone agree with any of it. It is not enough (it is downright wrong) for a scientist to hypothesise that X might be present in vaccines and that vaccines might provide a delivery system - as for example Mikovits did speculate on air in the first boradcast on Nevada TV and later if I am correct. A scientist has to prove it and that evidence has to stand up to scrutiny. You seem to want everyone to acknowledge the possibility however slight however unlikely even if it currently is impossible but might one day become viable - simply because there's a minuscule chance. Until such time as one of these family of viruses or any virus is connected to human infection and human disease - all the vaccine manufacturers can do if they think a risk exists is heighten their safety protocols and look for better ways of controlling biohazards. But evidence of specific human risk has to come first and thus far it ain't. Don't mean it won't but it ain't yet happened and wishing it so don't make it so.

 

[currer]

I won't claim to understand much of what you are saying Natasa let alone agree with any of it. It is not enough (it is downright wrong) for a scientist to hypothesise that X might be present in vaccines and that vaccines might provide a delivery system - as for example Mikovits did speculate on air in the first boradcast on Nevada TV and later if I am correct. A scientist has to prove it and that evidence has to stand up to scrutiny. You seem to want everyone to acknowledge the possibility however slight however unlikely even if it currently is impossible but might one day become viable - simply because there's a minuscule chance. Until such time as one of these family of viruses or any virus is connected to human infection and human disease - all the vaccine manufacturers can do if they think a risk exists is heighten their safety protocols and look for better ways of controlling biohazards. But evidence of specific human risk has to come first and thus far it ain't. Don't mean it won't but it ain't yet happened and wishing it so don't make it so.

Mikovits never said anything publicly about vaccines Firestormm.

You are confusing her with Jamie Deckoff Jones who did speculate this way on her blog.

 

[Firestormm]

Nevada Newsmakers: Thursday 8 October 2009: http://nevadanewsmakers.com/video/default.asp?showID=938

If the video doesn't appear at the link simply search the archives for Mikovits and it's the first one.

It is interesting to sometimes review what was said albeit with the benefit of hindsight. The speculation about vaccines and the unpublished revelation about autism is at 28 minutes or so from Mikovits. You are correct however, she didn't speculate that vaccines harboured this virus but that vaccines might somehow trigger the virus that was already in the immune system or 'amplified it' creating some sort of immune deficiency.

Interesting again to note that even before the break Annette is looking rather concerned, and when they come back Annette 'wants to clear something up about vaccines' namely that they are not saying don't vaccinate or 'I don't think either of us is saying vaccines cause autism', but rather they hope the development of something that would target the XMRV would enable vaccines to function more safely.

Sorry my timer on the video doesn't allow me to let you know the precise times things were said. But once you get past the adverts it isn't very long.

 

[alex3619]

Based on recent models of ME such as what Maes is producing, its very much a concern that vaccines can trigger ME or exacerbate ME. This would fit with many pathogens, not just MLVs. This does not make vaccines any more dangerous than the diseases they prevent, but it puts the onus on doctors to test patients to ensure that the vaccine will be safe for an individual patient, which would massively increase the cost of delivering vaccines.

Personally I think that vaccines should be rarely used in ME patients, and live vaccines should only be used if the patient is at imminent risk of contracting something lethal.

Bye, Alex

 

[natasa778]

... Until such time as one of these family of viruses or any virus is connected to human infection and human disease ...

the whole point of my post is that most of those who should be checking for those connections are doing their best to look in all the wrong places, very much hoping that the whole thing will be forgotten soon, let alone connect anything to anything. It would be like opening the car trunk in order to check the car engine for suspected faults. Looking for the murder weapon on suspected killer's kitchen table, not finding it there and abandoning the search If this wasnt about peoples lives it would be hillarious, in the best of Pink Panther detective tradition.