XMRV: Necessary but not sufficient?

[gracenote]

double-blind study

From the article Chronic Fatigue and Prostate Cancer: A Retroviral Connection by Sam Kean

"One has to be very careful about making claims about such a sensitive and emotionally charged issue as CFS, where many claims have been made in the past." At the least, a double-blind study where a third-party lab searches for XMRV in CFS patients and in controls is vital, he [DeRisi] says.

Isn't this what we all are hoping will happen? Isn't this what is needed to move this research to the next step? I hope someone, somewhere is trying to do this now. I don't know that we need to characterize DeRisi as someone protecting his turf/discovery, at least based on this one statement.
----------
According to what Kurt just posted above, it looks like many someones, somewheres, are already beginning these studies.

 

[jenbooks]

Suggesting her results could be due to contamination is an insult and I read it as protecting his turf and not wanting her to steal his thunder.

 

[gracenote]

okay, got it

Jenbooks said:

Suggesting her results could be due to contamination is an insult and I read it as protecting his turf and not wanting her to steal his thunder.

Okay, I guess I just passed over this part: "And the Mikovits team didn't do enough to rule out contamination, he [DeRisi] says." I get it. That makes sense.

 

[George]

Here are some that people have posted or that I have heard about back channel (hope it is OK to post these):

Dr. Kerr in the U.K.
Dr. LLoyd in Australia
Prof. Towers at University College London
Dr. Coffin at Tufts University, Boston, MA, USA
Dr. Paul Jolicoeur The University of Montreal, CA
Retroviral research group at the CDC Virology Lab in Atlanta, GA, USA

As this is competitive, some of these labs will be trying to get reports out quickly. I know of one additional private study underway that is close to reporting, and suspect there may be quite a few more that are keeping quiet. The CDC has a head start.

Thanks for posting that Kurt. I've been searching daily for research. study's, or information about who is doing what. They really are all very low key about this. I am keeping my fingers crossed for a confirmation of XMRV in a significant percent of PWC's.

 

[_Kim_]

Some already published; just not on CFS yet.
http://www.urotoday.com/61/browse_c...ially_highgrade_tumors__abstract10302009.html

That study is from Ila Singh's lab at the University of Utah. She's been studying XMRV for some time now. Her images were used in many of the XMRV articles that the press has been publishing in connection to the WPI Science article.

 

[kurt]

Singh found no RNasL connection !!!!! ????

That study is from Ila Singh's lab at the University of Utah. She's been studying XMRV for some time now. Her images were used in many of the XMRV articles that the press has been publishing in connection to the WPI Science article.

WOW, thanks for pointing that out. Am I reading this correctly? Looks like Singh found no RNAsL connection in her study!!!???

Here is the abstract:

XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors - Abstract Show Comments PDF Print E-mail
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Friday, 30 October 2009

Department of Pathology and Cell Biology, Columbia University Medical Center, 622 West 168th Street, New York, NY 10032, USA.

Xenotropic murine leukemia virus-related virus (XMRV) was recently discovered in human prostate cancers and is the first gammaretrovirus known to infect humans. While gammaretroviruses have well-characterized oncogenic effects in animals, they have not been shown to cause human cancers. We provide experimental evidence that XMRV is indeed a gammaretrovirus with protein composition and particle ultrastructure highly similar to Moloney murine leukemia virus (MoMLV), another gammaretrovirus. We analyzed 334 consecutive prostate resection specimens, using a quantitative PCR assay and immunohistochemistry (IHC) with an anti-XMRV specific antiserum. We found XMRV DNA in 6% and XMRV protein expression in 23% of prostate cancers. XMRV proteins were expressed primarily in malignant epithelial cells, suggesting that retroviral infection may be directly linked to tumorigenesis. XMRV infection was associated with prostate cancer, especially higher-grade cancers. We found XMRV infection to be independent of a common polymorphism in the RNASEL gene, unlike results previously reported. This finding increases the population at risk for XMRV infection from only those homozygous for the RNASEL variant to all individuals. Our observations provide evidence for an association of XMRV with malignant cells and with more aggressive tumors.

Written by:
Schlaberg R, Choe DJ, Brown KR, Thaker HM, Singh IR.

 

[_Kim_]

Kurt, that is an Open Access article. You can read the full text from the link below.

XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors

XMRV Infection Is Independent of the R462Q Polymorphism of RNASEL.

XMRV was initially discovered in prostate cancers from men homozygous for a common variant of the antiviral enzyme RNase L. This R462Q amino acid substitution results in a 3-fold reduction of enzymatic activity (8). In their study of 86 men with prostate cancer, Urisman et al. reported that 89% of XMRV-positive cases were homozygous for the R462Q variant (QQ) as compared to 16% of XMRV-negative cases (6). We profiled our 334 cases for the RNase L R462Q variant. The distribution was similar between cases with prostate cancer and controls (42.9% RR, 47.2% RQ, and 9.9% QQ in cancers vs. 52.5% RR, 40.6% RQ, and 6.9% QQ in controls, Fig. 4E). There was also no difference in allelic distribution between XMRV PCR-positive (50% RR, 43% RQ, and 7% QQ) and PCR-negative cases (42.7% RR, 47.4% RQ, and 10% QQ; Fig. 4E). The 2 XMRV-positive controls had RR alleles. When IHC was used to define XMRV-positive and -negative cases, the relative allelic distributions were also similar. We thus found no association between the presence of XMRV and the RNase L R462Q variant.

 

[_Kim_]

earlier XMRV publication

And here is the 2008 Silverman publication:


Integration Site Preference of Xenotropic Murine Leukemia Virus-Related Virus, a New Human Retrovirus Associated with Prostate Cancer

Sanggu Kim,1 Namshin Kim,3,{dagger} Beihua Dong,5 David Boren,2 Serena A. Lee,2 Jaydip Das Gupta,5 Christina Gaughan,5 Eric A. Klein,6 Christopher Lee,3 Robert H. Silverman,5 and Samson A. Chow1,2,3,4*

 

[Martlet]

I'd guess: almost certainly yes, jenbooks, it's possible because XMRV could be in their blood. They could have picked it up from a mouse perhaps? Lots of anecdotal accounts out there from people with cats who had flea bites just before they got sick. Including, that would figure with the 3 people in my family (inc myself) who all got sick at roughly the same time.

My guess would be yes, too. I was traveling out West when I got sick and a tick bite was certainly possible. I remember they tested me for Rocky Mountain Spotted Fever, in an attempt to rule things out.

That said, I had a dog, while one friend had a dog and guinea pigs and another had a cat, so fleas also sound like a very possible vector.

And if the virus was already in the human population, the flea or tick could transfer it straight from person to person, without needing a mouse.

 

[Marylib]

"Mystery illnesses" throughout history

I am no scholar...but it is interesting to speculate how many illnesses have turned out to result from infection. The "plague," (who would have thought it was the flea bites from the rats?), tuberculosis, stomach ulcers, you name it.
I think one day we will look back at ME/CFS as one of those, won't we? And someday perhaps, the intervention of psychiatry in this illness will be likened to the practice of "casting out spirits" to cure the ill.

 

[George]

XMRV is not a new new illness

HIV entered the Human Gene pool between 1890 and 1915 it took around 70 years for it to become a pandemic. Remember it's passed on via sexual secretions and blood like XMRV.

The XMRV virus likely entered the population between 1910 and 1930. It's not a new new illness. Most researchers in the CFS field put the first epidemic at 1934 in LA General Hospital.

If you have more or less the same time frame for spread in the population, roughly70 years, then the 80's and 90's would be when it became to "big" to be ignored. Enough people have the virus at this point that like HIV it's a pandemic.

If you want to follow the ideology that I state above please look in the General section under the question about outbreaks.Warning! It's a really long read( big grin)

 

[George]

Right on

I am no scholar...but it is interesting to speculate how many illnesses have turned out to result from infection. The "plague," (who would have thought it was the flea bites from the rats?), tuberculosis, stomach ulcers, you name it.
I think one day we will look back at ME/CFS as one of those, won't we? And someday perhaps, the intervention of psychiatry in this illness will be likened to the practice of "casting out spirits" to cure the ill.

Hey Marylib you got it right on. My daddy died from all of the stomach surgeries. He had ulcers that kept bleeding. So the doctors took out more and more of his stomach. He died at the age of 53 from malnutrition. That was in 1986. The doctors hounded him about "being positive", "not stressing" and other things that they believed at the time caused ulcers. Not 5 years later some smart doctors said, "wow, look at that it's a bacteria that caused the problem, not worry like we use to think"

Sheesh! And this happened in my life time. So it's not really unusual what's happening with us. It's part of pattern that really does go back to casting out demons like you say. We can be a superstitions lot sometimes.

Sometimes I wonder if the Psychiatrist are really twisted people who can't separate from their egos long enough to do "pure science". They are too busy needing to be right.

 

[Marylib]

For George

Certainly I feel psychiatrists have not been helpful in treating ME/CFS..and even in some cases have possibly done great harm, but I sure can't label them all as egotists.
I actually was sent to the psychiatrist before being diagnosed properly (by our wonderful NZ specialist, Dr Ros Vallings). The GP thought I had depression, of course.
It worked out okay for me, because I needed some kind of sleeping medication rather desperately and the GP was of no help. The psychiatrist doc I saw was a sweet older gentleman who indeed gave me some sleeping medication, which helped alot. He gave me an antidepressant, which did not help. So I quit taking it. Pretty simple.
Anyway, I liked him. I found him to be a sweet man who genuinely wanted to help me. Fortunately I was not severely ill, not in the UK, so was never in danger of being abused.
Fortunately I eventually found Dr Vallings.

 

[Marylib]

For George

Certainly I feel psychiatrists have not been helpful in treating ME/CFS..and even in some cases have possibly done great harm, but I sure can't label them all as egotists.
I actually was sent to the psychiatrist before being diagnosed properly (by our wonderful NZ specialist, Dr Ros Vallings). The GP thought I had depression, of course.
It worked out okay for me, because I needed some kind of sleeping medication rather desperately and the GP was of no help. The psychiatrist doc I saw was a sweet older gentleman who indeed gave me some sleeping medication, which helped alot. He gave me an antidepressant, which did not help. So I quit taking it. Pretty simple.
Anyway, I liked him. I found him to be a sweet man who genuinely wanted to help me. Fortunately I was not severely ill nor in the UK, so I never had to endure what some people have experienced.

 

[dannybex]

HIV entered the Human Gene pool between 1890 and 1915 it took around 70 years for it to become a pandemic. Remember it's passed on via sexual secretions and blood like XMRV.

The XMRV virus likely entered the population between 1910 and 1930. It's not a new new illness. Most researchers in the CFS field put the first epidemic at 1934 in LA General Hospital.

If you have more or less the same time frame for spread in the population, roughly70 years, then the 80's and 90's would be when it became to "big" to be ignored. Enough people have the virus at this point that like HIV it's a pandemic.

If you want to follow the ideology that I state above please look in the General section under the question about outbreaks.Warning! It's a really long read( big grin)

So in other words, it's likely not very easy to "catch" it, even if you're just talking about the outbreaks. I would be curious to know where the you got the HIV information...even though HIV and XMRV are totally different retroviruses.

d.

 

[kurt]

ticks and retrovirus

My guess would be yes, too. I was traveling out West when I got sick and a tick bite was certainly possible. I remember they tested me for Rocky Mountain Spotted Fever, in an attempt to rule things out.

That said, I had a dog, while one friend had a dog and guinea pigs and another had a cat, so fleas also sound like a very possible vector.

And if the virus was already in the human population, the flea or tick could transfer it straight from person to person, without needing a mouse.

See the study abstract below. While the authors conclude that HIV transmission by ticks is unlikely, they demonstrated that the HIV retrovirus stays alive for up to 10 days inside the tick... XMRV is a much simpler retrovirus than HIV, so don't know if that means it is more or less likely to survive that long.

Evaluation of mechanical transmission of HIV by the African soft tick, Ornithodoros moubata

Humphery-Smith, Ian; Donker, Ghislaine; Turzo, Alexandre; Chastel, Claude; Schmidt-Mayerova, Helena

Objectives: To assess the ability of the African Hut Tampan, Ornithodoros moubata, to mechanically transmit HIV-1 and to re-appraise HIV-1 infectivity in an arthropod cell line at 28 and 35 [degrees]C.

Design: To evaluate HIV-1 transmission by O. moubata, as determined by HIV-1 survival 'blood-meal' size and interval between feeds, various tick developmental stages were allowed to feed on a heavily infected lymphoblast-rich blood-meal containing HIV-1BRU in an in vitro feeding chamber.

Methods: Blood-meal regurgitation was evaluated using 51Cr-labelled human erythrocytes, and human lymphoblast survival in ticks using Trypan blue. HIV-1 survival in ticks was evaluated by reverse transcriptase activity in tick homogenates cocultured with CEM lymphoblasts. Polymerase chain reaction and Southern blot analysis were used to detect proviral HIV-1 in arthropod cells in vitro.

Results: HIV-1Bru remained viable for up to 10 days within O. moubata adults. This is the longest recorded survival of HIV in an arthropod. In agreement with other studies, O. moubata regurgitated part of its previous blood-meal into the feeding lesion. Human CEM lymphoblasts partially survived for up to 7 days at 28 and 35[degrees]C inside O. moubata's digestive tract. The blood-meal of adult female ticks was as high as 240 [mu] (approximately 70 times more than a mosquito), while the most likely potential mechanical vectors (fourth- and fifth-stage nymphs) ingested an average of 39 [mu] (maximum, 73 [mu]l), with some ticks re-feeding as early as 14 days postfeed in the absence of a moult. Shortcomings associated with the experimental protocol suggest that HIV survival within O. moubata may reach 14 days following natural infection, or that ticks might re-feed earlier. Although HIV-1BRU and HIV-1NDK were unable to replicate at 28 and 35[degrees]C in CD4- Aedes albopictus C6/36 mosquito cells, HIV-1NDK was detected in its proviral form.

Conclusions: Our investigations showed that mechanical transmission of HIV-1 by O. moubata is unlikely to occur in the laboratory. This may not be the situation under field conditions.

http://journals.lww.com/aidsonline/...n_of_mechanical_transmission_of_HIV_by.6.aspx

 

[George]

So in other words, it's likely not very easy to "catch" it, even if you're just talking about the outbreaks. I would be curious to know where the you got the HIV information...even though HIV and XMRV are totally different retroviruses.

d.

Hi
You are right that they are very different retroviruses. I've been reading Dr. Coffins research on about a dozen different Murine Leukemia viruses. They are fascinating! No wonder this guy is interested in XMRV. Most of them are like you point out "not easy to catch". Most are blood born and don't survive long outside of that environment.

Oh my primary source of the HIV origins information is from here but I have a couple of others as well if you are interested.

http://www.avert.org/origin-aids-hiv.htm

 

[Advocate]

Oh my primary source of the HIV origins information is from here but I have a couple of others as well if you are interested.

http://www.avert.org/origin-aids-hiv.htm

Hi George,

That paper on the origins of HIV is very interesting. I think we have a lot to learn from HIV.

 

[Advocate]

Suggesting her results could be due to...

Suggesting her results could be due to contamination is an insult and I read it as protecting his turf and not wanting her to steal his thunder.

Isn't it strange how two-thirds of the tests for the sick people were contaminated but less than 4% of the healthy control tests were contaminated?

 

[Alice Band]

Kurt,

There is also a Spanish group to add to the list

http://www.institutferran.org/fatiga_cronica.htm

RESEARCH PROJECT

Second validation of the presence of retrovirus XMRV in patients with Syndrome of serious Chronic Fatigue (Fukuda criteria and Canadian positives - certificates by an expert doctor, demonstrable neurocognitivo impact and tests of effort test-retest (24h) with fall superior to 25% in a second and minimum of an analytical alteration of immune profile), and healthy population.
Selection of 100 patients and 100 healthy controls. Totally gratuitous study.

The patients will receive their results two months after the extractions of the samples.

More information: Mrs Lurdes Farreras (935522747). Beginning of the present study: January of 2010

Note

They say there is the possibility of testing for the XMRV Virus at their Institute but that the test is for the moment only experimental because there isn't enough scientific evidence that the test is reliable