Saturday, October 17, 2009

More Vindication!

  Bron: ME Research UK (Merge)
Datum: 16 oktober 2009
URL: http://www.meresearch.org.uk/information/publications/xmrvfind.html
Ref: Eerder op het ME-NET,

https://listserv.surfnet.nl/scripts/WA.EXE?S2=3DME-NET&X=3D&Y=3Dpublic@combi=dom.com&I=3D1&a=3D2009&q=3DXMRV

XMRV and ME/CFS - A stunning find
---------------------------------

The discovery of a potential retroviral link to ME/CFS, which is
estimated to affect some 17 million people worldwide, has certainly
caught the world's attention - no bad thing for an under-researched
and often-overlooked illness!
The scientific report, entitled
'Detection of infectious retrovirus, XMRV, in the blood cells of
CFS patients', appeared online in Science, one of the most prestigious
scientific journals in the world, on 8th October 2009 and described
the findings of a consortium of researchers from the Whittemore
Peterson Institute (WPI, located at the University of Nevada, Reno),
the National Cancer Institute (part of the National Institutes of
Health) and the Cleveland Clinic, Ohio.

The findings

The headline finding of the research paper was that DNA from a human
gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV),
could be detected in the peripheral blood mononuclear cells of 68 out
of 101 ME/CFS patients (67%) compared with only 8 out of 218 healthy
controls (3.7%). The extent of this difference in proportions is
unusual,
as it is the norm for scientific researchers to find
relatively small yet significant differences between patients and
closely matched control groups; in the modern world, novel associations
of such magnitude are rarely found between long-standing chronic
illnesses and infectious agents. In addition to the headline finding,
the researchers determined that XMRV proteins were being expressed in
blood cells from ME/CFS patients at very high levels compared with
controls, and through cell culture experiments they showed that
patient-derived XMRV was infectious and transmissible. So, as well as
being the first to show infection with this novel virus in ME/CFS
patients, the researchers appear to have been the first to be able to
isolate XMRV particles from the blood, and to show direct transmission
of this virus between blood cells - dramatic observations indeed.

What has caught the attention of the scientific world is that these observations seem to fit neatly, at least at a first glance, with what is already known about ME/CFS as a chronic illness. For example,
viruses related to XMRV have been reported to be involved in damage to
blood vessels and nerves, and natural killer cells (historically low
in ME/CFS) are said to be susceptible to infection by XMRV. Also, the
fact that retroviruses like XMRV are known to be able to activate some
other (latent) viruses might explain why ME/CFS has been associated
with a range of different viral triggers, such as herpesviruses like
Epstein-Barr, over the years. Again, as Dr Judy Mikovits and colleagues
point out in their paper, some of the most commonly reported features
of ME/CFS include neurological symptoms and immune dysfunction with
inflammatory cytokine and chemokine upregulation, and some of these
observations could be accounted for by infectious XMRV in lymphocytes.
The fact that such pieces seem to fit so well together is suggestive
only at this stage, however, and a virologist at Tufts University was
surely wise to say in New Scientist that while it's not impossible
that infection with this agent might cause a disease with neurological
and immunological consequences, we don't know for sure as yet.

The background

The scientific journey towards this discovery is an extremely
interesting one, and includes several strands: prostate cancer, the
RNAse L immune pathway, the discovery of the novel virus XMRV, and
ME/CFS. XMRV is a human retrovirus similar to HIV, HTLV-1 and a group
of endogenous murine leukaemia viruses found in the genomes of wild
mice (see the informative presentation on retroviruses by Dr Jones
of SAIC-Frederick/NCI-Frederick), and was first identified only in
2006 by Prof. Robert H. Silverman of the Cleveland Clinic, a co-author
on the 2009 ME/CFS study. Prof. Silverman initially showed the
presence of XMRV in prostate cancer tissue samples (PLoS Pathog,
2006), and subsequent work has confirmed XMRV protein expression in
23% of 334 prostate cancer biopsies (Proc Natl Acad Sci USA, 2009).
Importantly, the men with prostate cancer initially studied by Prof.
Silverman all had a specific genetic defect in their antiviral
defences, the RNase L antiviral pathway which Prof. Silverman had
been studying for 30 years, a lifetime's work of scientific
progression described in his fascinating essay, 'Journey through
the 2-5A/RNase L System'.

RNase L is the terminal enzyme in the 2,5A synthetase/RNase L
antiviral pathway, and plays an essential role in the elimination
of viral mRNAs. The enzyme has been the focus of research interest
in ME/CFS patients for nearly 20 years, and deregulation of this
pathway in subsets of ME/CFS patients has been reported extensively
in the scientific literature
(reviewed by Nijs and Fremont, 2008).
In ME/CFS, a wide spectrum of 'cleavage' of RNase L can be observed
(a phenomenon also seen in multiple sclerosis patients), and such
altered RNase L activity profoundly affects cellular physiology,
including apoptosis. Overall, an upregulated RNase L pathway in
ME/CFS is consistent with an activated immune state and a role for
persistent viral infection in the pathogenesis of the disorder -
and it is because of these and other findings that many researchers
have come to view ME/CFS as primarily a disorder of the innate
immune system
(see Klimas and Kineru, 2008). It was thanks to the
insight of Dr Judy Mikovits and her team at WPI that the potential
connection between RNase L dysfunction in XMRV-infected prostrate
cancer and in ME/CFS was recognised, and an exploration undertaken
to test for the presence of the virus in the banked blood samples
in the WPI tissue repository, the largest ME/CFS sample repository
in the world.

What we don't know

A plethora of unanswered questions arise from this discovery. Chief
among these concerns cause and effect: the researchers' work has
shown a suggestive, significant association between the presence of
XMRV and a diagnosis of ME/CFS, but this is far from proof that the
virus has a direct or even indirect role in the development or
maintenance of the illness. This and other points have been well-put
in a fine 'perspective' in Science by National Academy of Sciences
member and expert retrovirologist, Prof. John Coffin, and colleague
Jonathan Stoye, who say, 'There is still much that we do not
understand. Whether the virus plays a causative role in either
chronic fatigue syndrome or prostate cancer is unknown.'
They go on
to point out that XMRV infection might be higher, by co-incidence,
in the same locations as clusters of patients; that patients with
ME/CFS or prostate cancer might be more readily infected due to
immune activation; that XMRV might prefer to proliferate in cells
that are dividing rapidly, and that the presence of these cells in
these illnesses might simply make it easier to detect infection; and
that the mechanism of viral transmission remains unknown, as does
the prevalence or distribution XMRV in human or animal populations.
In the aftermath of all initial scientific reports of a potentially
major find, the unknown wildly exceeds the known - an exciting place
for ME/CFS research to find itself.

The next steps

The researchers say that since publication they have continued to
refine their test for XMRV, finding that 95% of 330 ME/CFS samples
have tested positive for XMRV antibodies in the plasma (showing
that these patients have at least been in contact with the virus
at some time). They plan to continue their in-depth studies of XMRV
to clarify its effects on the human immune system, and are
clinically validating a blood test for the detection of XMRV in
ME/CFS and other human diseases. And they will shortly begin the
work of determining if any currently approved drugs, such as AZT,
might be useful for suppressing XMRV. If these efforts are
successful, human clinical trials to determine the most effective
patient treatments in a clinical setting would surely be close
behind.

At the same time, other independent laboratories across the world
will be attempting to replicate the findings in their own local
populations of ME/CFS patients. Since the WPI researchers used
samples selected from several regions in the US where 'outbreaks
of CFS' had been documented (using patients diagnosed on CDC-1994
and 2003 Canadian Clinical criteria ), blood samples from patients
in other countries (possibly diagnosed with less stringent
criteria) might throw up very different results. Furthermore, it
will be particularly important for independent laboratories to
conduct double-blind studies to search for XMRV in ME/CFS patients
and healthy matched controls, to strengthen the evidence base as a
whole.

The long-term

This is a stunning find - like a comet from a cloudless sky to
patients across the world. Yet it is too early to know whether
the discovery will change the ME/CFS landscape or not. At worst,
the discovery will be just one of a number of false dawns that
have arrived over the years -- albeit one that has brought,
suddenly, the world's attention to a neglected field largely
ignored by mainstream biomedical medicine. In this scenario,
XMRV might prove to be simply a passenger virus carried by an
immune-depressed ME/CFS patient population, with little or no
influence on the illness. At best, however, XMRV might be found
to be the casual factor in the development and maintenance of
ME/CFS, and a combination of anti-viral drugs will be found to
eradicate the viral load from patients
. One consequence of this
'jackpot' scenario would be a demolition of the existing
diagnostic criteria for the 'syndrome' CFS (currently a ragbag
of common non-specific symptoms, with many causes, shared with
other illnesses), as well as the older criteria for myalgic
encephalomyelitis. These would be replaced by objective
diagnostic criteria based on state-of-the-art methodology -
surely a welcome liberation for both CFS and ME patients
currently parked in a Diagnostic Terminal. Indeed, the WPI group
has already suggested that a new disease entity - X associated
neuro-immune disease, or XAND - might arise from the rubble,
implying (one assumes) that the one-third of ME/CFS patients
found to be 'negative' for XMRV in the WPI report would also
acquire new, more appropriate diagnoses.

Like Dr Dan Peterson, medical director of the WPI, we are hopeful.
As he says, 'Patients with ME/CFS (XAND) deal with a myriad of
health issues as their quality of life declines. I'm excited
about the possibility of providing patients who are positive for
XMRV a definitive diagnosis, and hopefully very soon, a range
of effective treatment options.'


--------
(c) 2009 ME Research UK (Merge)

 

Thursday, October 15, 2009

Donate a quarter to help CDC buy a clue?

Hi all,

The Chronic Fatigue Syndrome Advisory Committee meeting in Washington,
D.C. is coming up on Oct. 29-30, and I know people were wanting to do
something as a form of protest against CDC's complete incompetance
towards CFS research for the past 20+ years.

I was thinking maybe if someone was going to CFSAC who felt like
giving out their address, people could send them letters with a
quarter in them to be given to CDC representatives to help them 'buy a
clue' in regards to the ongoing CFS epidemic which CDC's CFS Research
Program(CCRP) has treated as a sort of mass neurosis, even outright
hysteria for the cluster cases. Maybe a stand with a poster and a
basket could also be set up at the meeting- "Donate a quarter, help
CDC buy a clue."

If anyone is interested in being the point person on this or has a
different/better idea, such as a different address we could send them
to, email me off list or maybe just post your address so people can
start sending quarters. I just thought this way might get publicized.
Maybe after people speak they could walk to the CDC reps and place a
quarter on the table in front of them, I've never been to a CFSAC
meeting so I don't know the layout of the proceedings. Or maybe after
people speak they could throw a quarter in the basket. Just my .02, if
it sounds goofy then please disregard. I doubt the reps would accept
the 'donations', so any proceeds could be donated to WPI for good
accounting practices.

Take care,
Tate Mitchell  





Dr. Klimas on HIV versus CFS

Dr. Klimas:
My H.I.V. patients for the most part are hale and hearty thanks to three decades of intense and excellent research and billions of dollars invested. Many of my C.F.S. patients, on the other hand, are terribly ill and unable to work or participate in the care of their families.
I split my clinical time between the two illnesses, and I can tell you if I had to choose between the two illnesses (in 2009) I would rather have H.I.V.
* * *

This meshes with the Congressional testimony of Dr. Mark Loveless, an infectious disease specialist and head of the CFS and AIDS Clinic at Oregon Health Sciences University, who proclaimed that a CFIDS patient "feels every day significantly the same as an AIDS patient feels two months before death."

And I agree with Dr. Klimas -- I'd rather have HIV -- at least those patients get respect for what they accomplish, rather than constantly being called lazy and bullied about attempting the things they physically cannot do.

Readers Ask: A Virus Linked to Chronic Fatigue Syndrome

 

Was a C.F.S. Virus Discovered Years Ago?

Q.

Back in the early 1990s, Dr. Elaine DeFreitas at the Wistar Institute in Philadelphia discovered a novel human retrovirus (very closely related to HTLV 2, with Spuma-viruslike aspects) in C.F.I.D.S. patients. This was subsequently confirmed by two other prominent researchers (and a commercial laboratory).

Dr. DeFreitas was almost done sequencing its genes and published a meticulous paper in a top journal. Then the Centers for Disease Control and Prevention and the National Institutes of Health intentionally destroyed her reputation because it did not mesh with their vigorous assertions that C.F.I.D.S. was psychoneurosis. No one else has followed this up for fear that their career might likewise be destroyed. This was all detailed in the amazing book "Osler's Web."

Is this the same virus as the "novel" XMRV?
Justin Reilly

A.

Dr. Klimas responds:

Dr. DeFreitas was doing exciting work and should be congratulated for her early results suggesting retroviral infection in C.F.S. Since that time, technology has advanced in a dramatic way, giving investigators new tools to search for viruses that were yet to be identified in 1990-92, including the XMRV virus.

New antiviral drugs have also been developed that could potentially be effective in controlling this sort of infection. We also have a much stronger understanding of these drugs' toxicity and safe use.

I congratulate the Whittemore Peterson Institute researchers for their diligent work. I am also very happy for Elaine today. I would also ask patients to be patient a little bit longer so that researchers can devise and perform the sort of clinical trials that will let us know if this virus is the linchpin in continued illness.






One Click on XMRV

 Quacking Nonsense - NaturalNews.com
XMRV Virus And Chronic Fatigue Syndrome


A recently identified retrovirus called XMRV has been linked to the debilitating neuroimmune ME/CFS disease that affects more than one million people in the United States alone. Whereas it is a certainty that the pharmaceutical industry will be all over the XMRV virus and ME/CFS, it is disgraceful to maintain that the virus does not exist and that this new research is but a stalking horse for vaccines as Mike Adams of NaturalNews.com just has. It is not just dodgy psychiatrists who are suffering from scientific research exposure that have been making absolute fortunes out of these ME/CFS patients. Just whom is Mike Adams attempting to protect, we wonder? Before Adams publishes such arrant nonsense out on the internet, perhaps he should consider what a breakthrough this research has been for patients and their families before he quacks ever again.
Jane Bryant, The One Click Group
Related Links:
*
Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome
Judy A. Mikovits et al, 10.1126/science.1179052, Scienceexpress
*
Whittemore Peterson Institute Scientists Discover Significant link between XMRV and ME/CFS
Press Release, Whittemore Peterson Institute - Frankie Vigil, R&R Partners
*
Breakthrough Science For M.E. Millions After Decades Of Chronic Abuse And Neglect
Independent Leader & Steve Connor, Science Editor - The Independent
*
The New Journalism - Challenging The Status Quo
Jane Bryant, National Vaccine Information Center Conference Speech, United States of America






Wednesday, October 14, 2009

Mad As Hell Doctors: Eliminate health insurance and everyone wins

"American health care is a bizarre blend of the worst of capitalism and the worst of socialism," said Dr. Eugene Uphoff. "If money equated with health in America we would have the best system in the world."

Seward said that Americans must understand what single-payer is, and what it isn't.

"[Monies] directed to health insurance companies would be redirected into one, public fund that insures all Americans. It's not Socialism, it's smartism.

According to the Mad As Hell Doctors, if the insurance industry - the bureaucrats - are taken out of the health care equation, a single payer plan would pay for itself.

Dr. Paul Hochfeld, an emergency room physician in Corvalis, OR, who leads the doctor coalition, said "If we got rid of the 20 percent that's wasted by the insurance industry we'd have enough to cover everybody."

 

"18,000 Americans die each year from lack of proper health care,"
* * *
and who knows how many, like me, are left alive but disabled?




Should I Take the Swine Flu Vaccine???

 

 





CFS and Faith (or How the Church fails us....)

 
 

CFS AND FAITH IN THE SPOTLIGHT

Check out the October 18 issue of national weekly Christian magazine The Lookout for an article about CFS.  In "Always Tired," Writer Amy Hagberg describes the illness and its impact on the lives of four patients and notes that, "for many CFS patients, the lack of support from loved ones who barely acknowledge the reality of the affliction is as painful as the illness itself.  Unfortunately, the church isn't doing much better.  While the faith community is good at ministering to those who are grieving or have diseases like cancer, many ignore invisible illnesses like CFS.  But CFS is a real, complex illness that has both physical and psychiatric manifestations; it is not just depression or anxiety."
 
If you can't find a hard copy of the publication at your local bookstore or newsstand, you can read it online at www.lookoutmag.com.





 

Dear Sirs, I am sick....

According to Hillary Johnson, author of 'Osler's Web', the following
'letter' was written by a CDC staffer and was placed on a bulletin
board inside CDC for several years before being taken down due to
unwanted attention from a journalist. It provides a fair amount of
illumination on the Centers for Disease Control's attitude towards CFS
from the very beginning.


(original scanned document located at- http://oslersweb.com/files/Scan0001.pdf )

***************************************************************



                                     October 5, 1986



Center of Diseased Comptrollers
Bldg 6, Rm 127
Atlanta, GA 30333

Dear Sirs:

I am SICK. I saw your ad in the L.A. Times, and need your help. I am
so tired it took me 6 days to dictate this letter to my secretary.
Please send all available information, and I mean ALL, about CEBV,
CMV, HSV, VZV, HPV, HTLV III/LAV/HIV, RSV, HAV, HBV, SV40, G-BS, RSV,
RSVP, DRG's, OMB, FDA, NIH, INH, NIMH, SPBSQSA, ABC's, D&C's, T&A's,
S&M, ASPCA, UCLA, HMO's, AIDS, Ayds, USAID's, IUD's, BCP's, HBP, CHF,
ESRD, USAA, and Japanese Bee Encephalitis, PDQ. Also please send a
complete list of all physician's in the U.S., Canada, Mexico, the
Caribbean, South America, Europe, Africa, Asia (including the Indian
and Southeast Asian subcontinents), Greenland, Antarctica, and the
Marianas Islands who work with the above agents, along with their
addresses, telephone #'s, height, weight, hair and eye color, social
security #, number of living relatives, favorite colors, and how much
they charge (the more expensive, the better).

I would also like a list of recommended treatments for the above
conditions, in descending order of trendiness, including acyclovir,
gamma globulin, WXYZ-2, 3DPG, Vitamins A, B-1 thru 12, C, D, E, F, G,
H, I, J, K, L, M, N, O, P, and Q, Zinc, Cadmium, Cobolt, Neodymium,
Ytterbium, lecithin, morithin, lessismorithin, sensory deprivation,
walking on hot coals, alternating sensory deprivation and walking on
hot coals, purified fruit-bat guano injections, and bedrest. I have
already tried Valium, Lithium, Haldol, and thorazine, but they only
work when I take them.

Please, also inform me about how to get social security and workmen's
compensation for the above diseases. I have had them for over 40 years
now, and I am only 29 years old.

Thanks for all your help.



                                  I.M. Zappode

                                  2431 Western Blot

                                  Wornout, CA 98765



* * *
Would you want researchers with THAT attitude looking into YOUR disease?  If the researchers don't believe in it, are they really going to give it their all?
 
And the answer, for the past 25 years, has been No.  CDC staff made a number of jokes and snide remarks about patients being simply lazy or depressed or menopausal (disregarding the fact that a fair percentage were men and children who couldn't possibly be menopausal).
 
When Elaine De Freitas, a patient-funded researcher, found a retrovirus, CDC repeatedly claimed they couldn't replicate her research.  She repeatedly tried to help them replicate it, even sending them properly-mixed solutions.  Finally, she discovered that after telling them specifically that the blood samples she was sending should not be frozen because this would destroy the virus ... the blood samples were being stored in the freezer for several weeks!  It became apparent that CDC didn't WANT to find anything.
 
If they'd found something, they would have had to admit that their leader was wrong in attributing the problem to psychiatric reasons.  When Straus left the agency, he hand-picked Reeves to be his successor, and Reeves, too, has continued to attribute the problem to psychiatric factors, despite mounting evidence of a biologic basis.  The level of denial exhibited by both Straus and Reeves hasn't been seen since the Flat Earth Society!  Like Straus, Reeves will go to his grave insisting that he's right, we're just lazy and crazy, that the biological basis patients claim has never been proven to his satisfaction.  It's like trying to argue with a brick wall ... though you might be more successful with a brick wall, because you can always bring in a wrecking ball and knock it out of the way!
 
This is the abuse to which patients have been subjected for a quarter-century by the very people who are supposed to help them.
 



Monday, October 12, 2009

Latest DIRECTLY from WPI

Thank you for your interest in the Whittemore Peterson Institute and our new research findings on XMRV.  We have been overwhelmed with both your encouraging comments and the volume of email and traffic to our web site.  We are working on answering many of the general questions posed in the last few days.  Individual specific questions will be evaluated and responded to as appropriate.

- XMRV Testing:      The number one request has been ?how do I get tested for XMRV??  The WPI is negotiating an agreement with a clinical laboratory to allow for limited testing.  These limited test services will be made available as soon as possible and we will provide information on this website as to how the test can be requested.  We cannot offer individual testing and results from our research lab.  Please check back to our website for updates.

- Research Studies:   If you are interested in possibly being selected to participate in ongoing or future WPI research studies, we are working on an interactive form for our website.  It should be available in the next few days, and we encourage you to complete the form at Whittemore Peterson Institute for Neuro-Immune Disease.  While every study has specific requirements and not all who volunteer will be accepted, your willingness to participate is both crucial and deeply appreciated.

- Becoming a Patient:      WPI is currently constructing our new home on the campus of the University of Nevada School of Medicine.  It will open in the summer of 2010.  At this time we are not able to accept patients, but would be happy to add your name to our interest list.  With the rapid pace of research discoveries, we hope that there will be new treatment and diagnostic options available when we celebrate the opening of the new building.

The discovery of XMRV in ME/CFS patients opens an entire new avenue of neuro-immune disease research and our discovery has brought to this field world-renown immunologists and retrovirologists.  Our team of collaborators is working daily to translate our discoveries into new treatments as soon as possible. 

The discovery also raises many new questions about the role of XMRV in these diseases, how it is spread, what new or existing treatments may help combat the virus, and how treating the virus might improve the health of patients.  For access to what we know to date, please see our XMRV Q&A.  We will update it regularly and keep you informed. 

Whittemore Peterson Institute - XMRV Q & A

We know many of you have been waiting years for answers, accurate diagnoses and some kind of effective treatments.  All of us are dedicated to finding these, and we will continue to work as hard and as quickly as possible.  Please remain hopeful, and keep in contact with us via the website or email.  Making sure we have all of your contact information will ensure we are able to contact you with further information as it becomes available to us.

Angelina Gordon





A new virus for old diseases?

Perspective

A New Virus for Old Diseases?

Journal: Science  [Online October 8, 2009]

Authors: John M. Coffin [1] and Jonathan P. Stoye [2]

Affiliations:
[1] Department of Molecular Microbiology, Tufts University, Boston,
MA 02111, USA. E-mail: john.coffin@tufts.edu
[2] National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.

NLM Citation: PMID: 19815721


A retrovirus associated with cancer is linked to chronic
fatigue syndrome.

There is little consensus in the medical community on
whether chronic fatigue syndrome is a distinct disease. As its
name implies, the condition is characterized by debilitating
fatigue persisting for many years, and it affects as much as
1% of the world's population. Although chronic inflammation
is often found in these patients, no infectious or toxic agent
has been clearly implicated in this disease, which is
diagnosed largely by excluding other conditions that cause
similar symptoms (1). In this week's Science Express,
Lombardi et al. (2) describe the detection of xenotropic
murine leukemia virus-related virus (XMRV) in about twothirds
of patients diagnosed with chronic fatigue syndrome.


Both laboratory and epidemiological studies are now needed
to determine whether this virus has a causative role, not only
in this disease, but perhaps in others as well.


Chronic fatigue syndrome is not the first human disease to
which XMRV has been linked. The virus first was described
about 3 years ago in a few prostate cancer patients (3), and
recently detected in nearly a quarter of all prostate cancer
biopsies (4). It has been isolated from both prostate cancer
and chronic fatigue syndrome patients, and is similar to a
group of endogenous murine leukemia viruses (MLVs) found
in the genomes of inbred and related wild mice. Although a
half century of studies on MLVs and other
gammaretroviruses have led to important discoveries on
which much of our current understanding of cancer rests,
there has been no clear evidence demonstrating human
infection with gammaretroviruses, or associating these agents
with any human disease.

Endogenous viruses, such as xenotropic MLV, arise when
retroviruses infect germline cells. The integrated viral DNA,
or provirus, is passed on to offspring as part of the host
genome (see the figure). Endogenous proviruses form a large
part of the genetic complement of modern mammals-about
8% of the human genome, for example. Xenotropic
proviruses first entered the mouse germ line about a million
years ago, but cannot infect cells of the mice that carry them
because of a mutation in the cellular receptor for the virus
presumed to have arisen after viral entry into the germ line.
The propensity of xenotropic MLVs to infect rapidly dividing
human cells has made it a common contaminant in cultured
cells, particularly in certain human tumor cell lines (5).

There is more than 90% DNA sequence identity between
XMRV and xenotropic MLV, and their biological properties
are virtually indistinguishable (6-9), leaving little doubt that
the former is derived from the latter by one or more crossspecies
transmission events. There are several lines of
evidence that transmission happened in the outside world and
was not a laboratory contaminant. One is that XMRVs from
disparate locations and from both chronic fatigue syndrome
and prostate cancer patients are nearly identical: The viral
genomes differ by only a few nucleotides, whereas there are
hundreds of sequence differences between XMRVs and
xenotropic murine leukemia proviruses of laboratory mice.
Other evidence includes the presence of XMRV and high
amounts of antibodies to XMRV and other MLVs in chronic
fatigue syndrome and prostate cancer patients.

There is still much that we do not understand. Whether the
virus plays a causative role in either chronic fatigue syndrome
or prostate cancer is unknown. For example, XMRV infection
might, coincidentally, be more frequent in the same
geographical region as a cluster of patients with chronic
fatigue syndrome. And individuals with either disease might
be more readily infected due to immune activation. XMRV
might prefer to grow in rapidly dividing prostate cancer cells
(10), and the presence of rapidly dividing cells in either
condition might make infection more readily detectable. We
do not know how the virus is transmitted, and the suggestion,
based on indirect evidence, that there is sexual transmission
(8) is premature. Given that infectious virus is present in
plasma and in blood cells, blood-borne transmission is a
possibility. Furthermore, we do not know the prevalence or
distribution of this virus in either human or animal
populations, and animal models for infection and
pathogenesis are badly needed.

Two characteristics of XMRV are particularly noteworthy.
One is the near genetic identity of isolates from different
diseases and from individuals in different parts of the United
States. The two most distantly related genomes sequenced to
date differ by fewer than 30 out of about 8000 nucleotides.
Thus, all of the XMRV isolates are more similar to each other
than are the genomes isolated from any one individual
infected with the human immunodeficiency virus. In this
respect, XMRV more closely resembles human T cell
lymphotropic viruses (HTLVs) isolated from the same
geographic region (11). As in the case with HTLV, the lack
of diversity implies that XMRV recently descended from a
common ancestor, and that the number of replication cycles
within one infected individual is limited.

Another notable feature of XMRV is that the frequency of
infection in nondiseased controls is remarkably high-about
4% in both normal individuals from the same geographic
region as infected patients with chronic fatigue syndrome,
and in nonmalignant prostates. If these figures are borne out
in larger studies, it would mean that perhaps 10 million
people in the United Sates and hundreds of millions
worldwide are infected with a virus whose pathogenic
potential for humans is still unknown. However, it is clear
that closely related viruses cause a variety of major diseases,
including cancer, in many other mammals. Further study may
reveal XMRV as a cause of more than one well-known "old"
disease, with potentially important implications for diagnosis,
prevention, and therapy.

References
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Published online 8 October 2009;
10.1126/science.1181349
Include this information when citing this paper.

Path to human infection. Although xenotropic murine
leukemia virus (MLV)-derived from exogenous MLVs that
became established as proviruses in the mouse germ line-
can no longer infect mice, it can infect humans, apparently
leading to one or more cross-species infection events to
become XMRV.