XMRV virus
 

Biologisch Medisch Centrum | MLV Virus gevonden bij patienten met het Chronisch Vermoeidheids Syndroom | Paul van Meerendonk Utrecht Epe


 

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Dec 2010 video xmrv Mikovits begin bij 3 minuten.

Video de Meirleir

FDA / Harvard / NIH onderzoek.

In deze studie analyseerden onderzoekers van de Food and Drug Administration, Harvard Medical School en National Institutes of Health 41 bloedmonsters van 37 patiënten met CVS. Zij vonden bij CVS-patiënten geen enkel spoor van het retrovirus XMRV, maar wel DNA van andere muizenleukemievirussen (MLV’s). Bij 32 daarvan vonden de onderzoekers DNA van MLV-achtige virussen in het bloed. Ze bekeken ook bloedmonsters van gezonde bloeddonoren en daar werden deze MLV-achtige virussen slechts bij 3 van de 44 bloeddonoren gevonden.
Het aantonen van virus-DNA bij CVS-patiënten wil nog niet zeggen dat deze virussen de oorzaak zijn van het vermoeidheidssyndroom, zo wordt in een begeleidend commentaar aangestipt. Om een oorzakelijk verband te kunnen aantonen zou men die virussen moeten kunnen toedienen, zoals dat gebeurde met het aantonen van Helicobacter pylori als de oorzaak van maagzweren. In het commentaar wordt wel voorgesteld om nu toch te starten met onderzoek naar het effect van antivirale middelen bij CVS-patiënten.


 

Als het retrovirus inderdaad ME/CVS veroorzaakt is er natuurlijk ook op een ander gebied nog een lange weg te gaan: het ontwikkelen van medicijnen om het virus te bestrijden. Want van een eenmaal opgelopen retrovirus, kom je niet meer af. Het is te verwachten dat grote farmaceutische bedrijven zich hierop zullen werpen. Met medicijnen is immers geld te verdienen. Tot nu toe hebben ME/CVS-patiënten van die kant weinig belangstelling ervaren.


Bestaan XMRV toch aangetoond in een nieuw onderzoek. Nu zijn ook varianten gevonden van de XMRV, iets wat normaal is bij virussen, en heeft de groep een andere naam gekregen namelijk MLV. Maar er is nog steeds onduidelijkheid over het XMRV virus omdat er onderzoeken zijn  geweeest met negatieve uitslagen en onderzoeken met een besmetting van bloedmonsters door hulpstoffen.

Dr. Mary Kearney van het National Cancer Institute (NCI), onderdeel van de NIH,  maakte melding van een nieuwe en uiterst betrouwbare XMRV-test. Het zou gaan om een zeer gevoelige test, die bovendien eventuele contaminatie (vervuiling) met muizen-DNA met 100% zekerheid kan detecteren.



Het is nu bij deze twee onderzoeken aangetoond dat bij CVS patienten de virussen veel meer  worden gevonden dan bij de controlle groep. 86.5% t.o. 6 %.

Nog niet zeker is of dit virus de CVS veroorzaak of dat de oorzaak ligt in het mogelijk zwakkere immuunsysteem.

Hiermee is wel duidelijker geworden dat het al langere tijd ingeslagen pad van anti virale behandeling en versterking van het immuunsysteem inderdaad de goede weg was naar oplossing van veel CVS gevallen.

 

Behandeling XMRV/MLV

Wat de behandeling betreft verwijst Dr. de Meirleir naar een onderzoek van Singh dat is besproken.

Singh heeft 45 medicijnen uitgetest en kwam tot de conclusie dat er enkele zijn die de groei beperken.

Raltegravir, Tenofovir en Zidovudine.

Volgens Dr. De Meirleir kan deze combinatie resistentie in de hand werken (?)

Dr. De Meirleir zei dat er nog geen patiënten waren die al ART hadden geprobeerd maar dat klopt niet.
Als je namelijk Jamie Deckhoff en haar dochter volgt op hun blog, dan zie je dat zij veel beter zijn momenteel. Zij gebruiken een cocktail van middelen. (HAART)


Cheney had in een persoonlijke communicatie laten weten dat hij goede resultaten boekte met Artesunate. Dit is een NFKappaB remmer.
 

“Het virus is al veel meer verspreid dan we dachten!” zegt de professor. “We moeten het overactive immuunsysteem afremmen. Het is een stabiel virus en anti-retroviralen zijn niet nuttig.” (???)
Minocycline (medicijn tegen acné) kan MS stoppen en heeft ook antivirale eigenschappen.


Prof. Dr. Kenny De Meirleir over XMRV/MLV

Het onderzoek naar MLV wordt momenteel in België overgedaan.
Er is ondertussen al bekend dat meer dan 50% van de patiënten het MLV hebben.


Volgens Dr. De Meirleir gaan de symptomen/klachten een grotere rol spelen dan het virus zelf. Denk aan de maag- en darmproblematiek. Hij haalt aan dat de viral load in een grote groep patiënten niet meer in grote dosissen aanwezig is. Daarom heeft hij geen goed oog op anti-retrovirale middelen en wil hij doorgaan met de bestaande therapieën die erop gericht zijn het immuunsysteem te herstellen.

Tweede grote studie die XMRV/MLV aantoond

 

The National Institute of Health along with representatives from the FDA and CDC held a telebriefing for the press regarding the possible link between XMRV and ME/CFS. The findings of the FDA and NIH showed that 86.5% of blood samples taken from ME/CFS patients (32 out of 37 samples) were found to be positive for variants of the XMRV virus, a retrovirus that is related to HIV This is in comparison with only 6% of a healthy control group (3 out of
44 samples).

This not only confirms the original findings tying the retrovirus to a large number of cases, it identified a host of infectious agents in the same family, called MLV-related viruses..MLV means "murine-leukemia virus," which is one of the 3 identified human retroviruses.  The M in XMRV stands for the same thing, and the R stands for "related."  MLV-related viruses all belong to the same family of retroviruses. 

This new finding of a diverse virus population is more consistent with what we know of retroviruses -- that they tend to mutate frequently, which makes them harder to eradicate.

 This is very big news for the ME/CFS community. It doesn't necessarily prove that the XMRV retrovirus causes ME/CFS, but the strength of this link is now beyond any doubt, and will mean that further studies
 

Eerste studie die XMRV aantoonde bij CFS

Nytimes October 8, 2009
 

Many people with CFS are infected with a little known virus that may cause or at least contribute to their illness, researchers are reporting.

The syndrome, which causes prolonged and severe fatigue, body aches and other symptoms, has long been a mystery ailment, and patients have sometimes been suspected of malingering or having psychiatric problems rather than genuine physical ones. Worldwide, 17 million people have the syndrome, including at least one million Americans.

An article published online Thursday in the journal Science reports that 68 of 101 patients with the syndrome, or 67 percent, were infected with an infectious virus, xenotropic murine leukemia virus-related virus, or XMRV. By contrast, only 3.7 percent of 218 healthy people were infected. Continuing work after the paper was published has found the virus in nearly 98 percent of about 300 patients with the syndrome, said Dr. Judy A. Mikovits, the lead author of the paper.

XMRV is a retrovirus, a member of the same family of viruses as the AIDS virus. These viruses carry their genetic information in RNA rather than DNA, and they insert themselves into their hosts’ genetic material and stay for life.

Dr. Mikovits and other scientists cautioned that they had not yet proved that the virus causes the syndrome. In theory, people with the syndrome may have some other, underlying health problem that makes them prone to being infected by the virus, which could be just a bystander. More studies are needed to explain the connection.

But Dr. Mikovits said she thought the virus would turn out to be the cause, not just of chronic fatigue, but of other illnesses as well. Previous studies have found it in cells taken from prostate cancers.

“I think this establishes what had always been considered a psychiatric disease as an infectious disease,” said Dr. Mikovits, who is research director at the Whittemore Peterson Institute in Reno, a nonprofit center created by the parents of a woman who has a severe case of the syndrome. Her co-authors include scientists from the National Cancer Institute and the Cleveland Clinic

Dr. Mikovits said she and her colleagues were drawing up plans to test antiretroviral drugs — some of the same ones used to treat HIV infection to see whether they could help patients with chronic fatigue. If the drugs work, that will help prove that the virus is causing the illness. She said patients and doctors should wait for the studies to be finished before trying the drugs.

Dr. William Schaffner, an infectious disease expert at Vanderbilt University said the discovery was exciting and made sense.

“My first reaction is, ‘At last,’ ” Dr. Schaffner said. “In interacting with patients with chronic fatigue syndrome, you get the distinct impression that there’s got to be something there.”

He said the illness is intensely frustrating to doctors because it is not understood, there is no effective treatment and many patients are sick for a long time.

He added, “This is going to create an avalanche of subsequent studies.”   End.

Again CFS/ME associated with a chronic viral infection
 

This is not the first time CFS/ME has been associated with a chronic viral infection - it used to be called "post-viral fatigue syndrome," after all. In studies, CFS/ME has been connected with a variety of different viruses, including:

•herpes viruses (especially Epstein-Barr virus, cytomegalovirus and HHV-6)
•enteroviruses (polioviruses, Coxsackie viruses, echoviruses)
•parainfluenza virus 5 (PIV-5)
•parvovirus B19
•various retroviruses



 

In January 2010, another research team found no evidence of XMRV in 186 patients with chronic fatigue syndrome in the United Kingdom. A third study, published earlier this month, also failed to identify XMRV in 170 patients.



 

A new study out of Germany could provide support for U.S. research linking XMRV to chronic fatigue syndrome and cast doubt on European studies failing to find it.

The German study didn't look into chronic fatigue syndrome, and it didn't involve the blood or prostate tissue, as other studies have. Instead, researchers tested respiratory-tract secretions from healthy controls plus 3 different categories of people with respiratory-tract infections (RTIs): those with no underlying conditions, those with underlying chronic obstructive pulmonary disease (COPD), and those on immunosuppressive medications because of a transplant.

They found XMRV in:

  • 3.2% of controls
  • 2.3% of those with RTIs & no underlying conditions
  • 2.3% of those with RTIs & COPD
  • 9.9% of those on immunosuppressive drugs

     
Onderzoeken naar XMRV:

http://www.ncbi.nlm.nih.gov/pubmed/19959199
Xenotropic murine leukemia virus related virus susceptible to AZT


http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011738
Apobec 3G Efficiently Reduces Infectivity of the Human Exogenous Gammaretrovirus XMRV
Kristin Stieler, Nicole Fischer
PlosOne, 2010 July 23

http://www.ncbi.nlm.nih.gov/pubmed/20576103
Identification of viral infections in the prostate and evaluation of their association with cancer.
Martinez-Fierro ML, Leach RJ, Gomez-Guerra L, Garza-Guajardo R, Pais-Johnson T, Beuten J, Morales-Rodriguez IB, Hernandez-Ordonez MA, Calderon-Cardenas G, Ortiz-Lopez R, Rivas-Estilla AM, Ancer-Rodriguez J, Rojas-Martinez A.
BMC Cancer.  2010 Jun 24

http://www.ncbi.nlm.nih.gov/pubmed/20507757
Xenotropic murine leukemia virus-related gammaretrovirus in respiratory tract.
Fischer N, Schulz C, Stieler K, Hohn O, Lange C, Drosten C, Aepfelbacher M.
Emerg Infect Dis.  Epub ahead of print 2010 Jun

http://jvi.asm.org/cgi/content/abstract/84/13/6288?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=arnold&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
Evaluation of Cellular Determinants Required for In Vitro Xenotropic Murine Leukemia Virus-Related Virus Entry into Human Prostate Cancer and Noncancerous Cells
Sushma Bhosle,1 Suganthi Suppiah,1 Ross Molinaro,1 Yuying Liang,1 Rebecca Arnold,2 William Diehl,1 Natalia Makarova,3 Jerry Blackwell,3 John Petros,1,2,5 Dennis Liotta,4 Eric Hunter,1,6 and Hinh Ly1*
Journal of Virology, July 2010. (published ahead of print 21 April 2010)

http://www.ncbi.nlm.nih.gov/pubmed/20507233
Characterization of retroviral and lentiviral vectors pseudotyped with XMRV envelope glycoprotein.
Sakuma T, Ravin SS, Tonne JM, Thatava T, Ohmine S, Takeuchi Y, Malech HL, Ikeda Y.
Hum Gene Ther. Epub ahead of print 2010 May 27.

http://www.ncbi.nlm.nih.gov/pubmed/20504941
Acutely transforming retrovirus expressing Nras generated from HT-1080 fibrosarcoma cells infected with XMRV.
Metzger MJ, Miller AD.
J Virol. Epub ahead of print 2010 May 26.

http://oham.cancer.gov/objects/pdf/2010ICMAOI_Program_Book.pdf
http://www.capconcorp.com/meeting/12thICMAOI/agenda.asp
Repeated Detection of Infectious Xenotropic Murine Virus-Related Virus (XMRV) in Human Neoplasia and Neuroimmune Diseases
Abstract from 12th International Conference On Malignancies In AIDS And Other Acquired Immunodeficiencies (ICMAOI)
April 26-27, 2010

http://www.ncbi.nlm.nih.gov/pubmed/20421928
Fidelity of target site duplication and sequence preference during integration of xenotropic murine leukemia virus-related virus.
Kim S, Rusmevichientong A, Dong B, Remenyi R, Silverman RH, Chow SA.
PLoS One. 2010 Apr 20

http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0009948
Raltegravir Is a Potent Inhibitor of XMRV, a Virus Implicated in Prostate Cancer and Chronic Fatigue Syndrome
Ila R. Singh1*, John E. Gorzynski1, Daria Drobysheva1, Leda Bassit2, Raymond F. Schinazi2
Plosone, April 1, 2010

http://www.ncbi.nlm.nih.gov/pubmed/20371060
XMRV infection in patients with prostate cancer: novel serologic assay and correlation with PCR and FISH.
Arnold RS, Makarova NV, Osunkoya AO, Suppiah S, Scott TA, Johnson NA, Bhosle SM, Liotta D, Hunter E, Marshall FF, Ly H, Molinaro RJ, Blackwell JL, Petros JA.
Urology. 2010 April

http://jvi.asm.org/cgi/content/abstract/84/5/2556
Xenotropic Murine Leukemia Virus-Related Virus Establishes an Efficient Spreading Infection and Exhibits Enhanced Transcriptional Activity in Prostate Carcinoma Cells ,
Jason J. Rodriguez and Stephen P. Goff*
Journal of Virology, March 2010 (published online 16 December 2009)

http://jvi.asm.org/cgi/content/abstract/JVI.00134-10v1
Inhibition of Xenotropic Murine Leukemia Virus-Related Virus by APOBEC3 Proteins and Antiviral Drugs
Tobias Paprotka, Narasimhan J. Venkatachari, Chawaree Chaipan, Ryan Burdick, Krista A. Delviks-Frankenberry, Wei-Shau Hu, and Vinay K. Pathak*
J. Virol. June 2010 (Published ahead of print 24 March 2010)

http://www.ncbi.nlm.nih.gov/pubmed/19959199
Xenotropic murine leukemia virus-related virus is susceptible to AZT.
Sakuma R, Sakuma T, Ohmine S, Silverman RH, Ikeda Y.
Virology, 2010 Feb 5 (Epub 2009 Dec 2)

http://jvi.asm.org/cgi/content/short/84/4/1874
The Prostate Cancer-Associated Human Retrovirus XMRV Lacks Direct Transforming Activity but Can Induce Low Rates of Transformation in Cultured Cells
Michael J. Metzger, Christiana J. Holguin, Ramon Mendoza, and A. Dusty Miller*
Journal of Virology, February 2010 (Published ahead of print 9 Dec 2009)

http://www.pnas.org/content/107/11/5166.abstract
Susceptibility of xenotropic murine leukemia virus-related virus (XMRV) to retroviral restriction factors
Harriet C. T. Grooma, Melvyn W. Yapa, Rui Pedro Galãob, Stuart J. D. Neilb, and Kate N. Bishopa,1
PNAS, 2010 Mar 16 (Epub 2010 Mar 1)

http://jvi.asm.org/cgi/content/abstract/JVI.01763-09v1
Androgen Stimulates Transcription and Replication of XMRV (Xenotropic Murine Leukemia Virus-Related Virus)
Beihua Dong and Robert H. Silverman*
J Virol. 2010 Feb (Epub 2009 Nov 11)

http://www.ncbi.nlm.nih.gov/pubmed/20142478
Retroviral infection in vivo requires an immune escape virulence factor encrypted in the envelope protein of oncoretroviruses.
Schlecht-Louf G, Renard M, Mangeney M, Letzelter C, Richaud A, Ducos B, Bouallaga I, Heidmann T.
Proc Natl Acad Sci U S A. 2010 Feb 23 (Epub 2010 Feb eight)

http://www.ncbi.nlm.nih.gov/pubmed/20110097
Host range and cellular tropism of the human exogenous gammaretrovirus XMRV.
Stieler K, Schulz C, Lavanya M, Aepfelbacher M, Stocking C, Fischer N.
Virology. 2010 Mar 30 (Epub 2010 Jan 27)


 
Kleine XMRV studie (16 patienten) en de daarbij opvallende verschijnselen in vergelijk met een referentiegroep:

Kenny De Meirleir M.D., PhD, Vrije Universiteit Brussel, Brussel, Belgium;

Marc Frémont, PhD;

K. Metzger, MS;

C. Roelant, PhD, RED Laboratories NV, Zellik, Belgium



RESULTS

 

The number of CD3+ T cells and CD57+ lymphocytes

was significantly lower

compared to the reference values.

 

C4a and elastase activity

were significantly higher

in the XMRV positive CFS population.

 

Soluble CD14

which codes for LPS in the plasma

was significantly higher

at p < 0.001 compared to the reference population.

 

XMRV positive CFS patients

had significantly higher

serum IL-10, MCP-1 , MIP-1 beta and IL-8 levels.

 

Serum levels of other cytokines

(IL-12, IL-1 beta, IL-6, TGF-beta and alpha-TNF)

were not statistically different

compared to the reference values.

 

Other lymphocyte subsets

showed

no difference from the reference in the XMRV positive patients.

 

Stool lgA and lgG3

were statistically lower

in the XMRV positive patients.

 

 

CONCLUSION

 

The results of this preliminary study in a limited number of subjects

show that XMRV positive CFS patients have

lower than normal levels of lymphocytes and low numbers of CD57+ lymphocyte subtype

as in HIV.

 

The absolute numbers of CD4+ and CD8+T cells

were not statistically different from the reference values,

but expanding this study to a larger number of patients is necessary

to make solid statements in this regard.

 

XMRV-positive CFS patients have an activated innate immune system

(elastase activity, increased C4a)

which could be related to microbial translocation

as their sCD14 is significantly higher than expected;

sCD14 strongly correlates with plasma LPS 1.

 

Low stool IgA (in some of these 16 patients it was undetectable)

also points towards a dysfunctional mucosa-associated lymphomal tissue (MALT)

in XMRV-positive CFS patients.

 

Furthermore we found that

these patients as a group have lower than normal lgG3 serum levels.

 

The cytokines IL-8, IL-10, MCP-1 and MIP-1beta are increased

and might constitute a biological signature for the viral infection.

 

These observations and others

(unpublished data on serum levels of LPS in CFS patients)

provide evidence for

microbial translocation

being part of

the pathophysiology

of XMRV positive patients.


 

No Evidence of Murine-Like Gammaretroviruses in CFS Patients Previously

Identified as XMRV-Infected

www.sciencexpress.org / 31 May 2011

Murine-like gammaretroviruses (MLVs), most
notably XMRV [xenotropic murine leukemia virus
(X-MLV)–related virus], have been reported to be
present in the blood of patients with chronic fatigue
syndrome (CFS). We evaluated blood samples from
61 patients with CFS from a single clinical practice,
43 of whom had previously been identified as
XMRV-positive. Our analysis included polymerase
chain reaction and reverse transcription polymerase
chain reaction procedures for detection of viral
nucleic acids and assays for detection of infectious
virus and virus-specific antibodies. We found no
evidence of XMRV or other MLVs in these blood
samples. In addition, we found that these
gammaretroviruses were strongly (X-MLV) or
partially (XMRV) susceptible to inactivation by sera
from CFS patients and healthy controls, which
suggested that establishment of a successful MLV
infection in humans would be unlikely. Consistent
with previous reports, we detected MLV sequences
in commercial laboratory reagents. Our results
indicate that previous evidence linking XMRV and
MLVs to CFS is likely attributable to laboratory
contamination.
 




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