RETROVIRUS XMRV and ME/CFS
WHAT DO WE KNOW SO FAR? AND WHAT DON'T WE KNOW?
Updated 24 October 2009
Presence of XMRV in the healthy population
what can we learn about the role of infection?
KEY FACTS ABOUT THE XMRV RESEARCH
KEY FACTS ABOUT RETROVIRUSES AND ME
This is a reprint of Dr Charles Shepherd’s article which appeared on the UK ME
Association Web site
This is a considerably extended and updated version of our first summary on XMRV
research. It includes additional information relating to questions that are
coming to the MEA about the research findings, in particular questions
concerning possible transmission and spread of XMRV, availability of private and
NHS tests for the virus here in the UK, possible treatment of XMRV with
antiviral drugs, and volunteering for UK research studies. We also report on a
new research study from Germany that has queried the link between XMRV and
prostate cancer.
This summary is intended to be a balanced account which not only raises
questions but is also very cautious when it comes to drawing any firm
conclusions about the role of XMRV at this very early stage in the research.
On Friday 9 October, the front page of the UK Independent newspaper carried a major news item under the heading, Has science found the cause of ME?
This referred to new research findings from America which indicate that a
recently discovered retrovirus, known as XMRV (xenotropic murine leukaemia
virus-related virus), could be playing an important role in causing or
maintaining ME/CFS.
The news item was accompanied by a very supportive editorial about the need for recognition and research into ME/CFS.
(The
news items can be read by clicking
HERE)
The Independent story was soon followed up by the rest
of the UK media, including the BBC.
Most of the news reports gave a reasonably balanced and accurate account of the
research. However, some reports incorrectly inferred that the cause of ME/CFS
had now been conclusively discovered and that an antiviral treatment would soon
be available.
A selection of UK media reports can be found in the
October news archive on the MEA website.
The actual research paper was published in the online edition of Science, along
with a perspective written by John Coffin (Department of Molecular Microbiology,
Tufts University, Boston, USA) and Jonathan Stoye (National Institute for
Medical Research, London).
These are potentially important research findings that could help with both the
diagnosis and management of ME/CFS. We congratulate all those involved in
deciding to do this research study.
However, a number of questions still have to be answered before anyone can
conclude that this virus plays a significant role in either the cause,
transmission, clinical assessment or management of ME/CFS.
The research has demonstrated a correlation between ME/CFS and XMRV – not that it is the causative infection.
Much more epidemiology and laboratory work now needs to be done to answer the
essential points set out below
1. Carrying out further and larger studies using different populations of people in different countries with ME/CFS. This work should include people at
different stages of the illness (to see if the virus is present in the same percentages in both early and late cases) and in all degrees of severity. Research
in
different countries is vital in view of the conflicting geographical findings
relating to XMRV in prostate cancer.
Using different international laboratories to test
for evidence of the virus.
Assessing what, if any, correlation there is
between the presence of this virus and (a) severity of symptoms, (b) a clear
infectious onset with a known infection, and (c) various other factors
involved in sub-grouping of people under the ME/CFS umbrella.
Assessing to what extent this virus is also
present in other chronic conditions, especially those such as multiple
sclerosis and lymphoma where viral infections have been implicated as a
causative factor.
Assessing whether this virus is acting as a benign
marker of disease or immune dysfunction, or is a
‘passenger virus’,
or whether it has a role in the actual disease
process and development of symptoms.
Investigating whether the presence of the virus in
healthy people acts as a predisposing factor in the development of ME/CFS
(possibly when another infective trigger appears) and/or prostate cancer
rather than being involved in the actual disease process.
Investigating what effect, if any, the virus has
in healthy people who carry it
over a period of time.
Assessing whether people with evidence of the virus should be treated with
antiretroviral medication, and if so developing a suitable antiviral drug
or combination of antiviral drugs.
Assessing whether animal model studies would help to increase our
understanding of the way in which this virus
may
infects cells and possibly
cause
disease.
Testing for XMRV
Until these research findings have been robustly replicated, and we have the
answers to some of the above questions, there is no point in asking your doctor
to be tested for XMRV.
This is because the NHS does not currently have the
facilities to do so and the testing procedures are only being used in a research
capacity at present.
But if it does turn out that there is a consistent and strong association with ME/CFS then testing for XMRV would almost certainly have to be made available.
We are not aware of any private pathology laboratories here in the UK that are
able to test for XMRV, or are intending to start offering this test. However
private testing is available in some countries outside the UK.
Viral transmission
We know
that
some
people with ME/CFS are very concerned about the possibility of transmission of
XMRV through what are termed body fluids (ie blood, saliva, semen).
However, until we know more about what this virus does
in the body it would be premature to start arriving at firm conclusions and
recommending all kinds of restrictions to normal daily living. Remember: we
still do not know for certain whether this is a disease-causing virus in humans
and whether it plays a role in causing or maintaining ME/CFS.
And if this virus was behaving as an ‘ME virus’ in the way that HIV, another
retrovirus, causes and transmits HIV infection, often leading to AIDS, there
would be a significant number of sexual partners of people with ME/CFS
developing ME/CFS – but this is clearly not the case.
One simple way of obtaining some early clues about viral transmission
of XMRV
would be
to test for the presence of the virus in healthy partners and offspring of
people who have the infection and comparing the findings to a control group of
people that have no such link.
Presence of XMRV in the healthy population
If this virus is also present in up to 4% of the normal healthy population here in the UK (ie around 2.4 million, or ten times the number of people who have ME/CFS), as appears to be the case in America, and it does play a significant role in diseases such as ME/CFS and prostate cancer, there will be widespread and very serious implications for public health, blood donation etc. This could also include vaccination against the virus and treating people who are XMRV positive. But these are complex decisions which can only be made in the light of further research studies.
In relation to blood donation in the UK, current advice is that people with ME/CFS who have symptoms, or are receiving treatment, should not donate blood. It would seem sensible in the short term, until we know more about transmission and pathogenicity of XMRV, to consider extending this restriction to people who have recovered from ME/CFS.
It seems strange that many overseas countries have not followed
the UK
lead on blood donation and ME/CFS.
What can we learn about the role of infection from outbreaks of ME/CFS?
It should be noted that unlike the retroviral infection HIV, ME/CFS is an
illness that occurs both sporadically and in highly localised acute geographical
outbreaks, often involving closed communities such as schools and hospitals,
where there is no obvious evidence of bodily fluid transmission. This fact would
obviously question the role of XMRV as a precipitating infection in the onset of
the illness.
In the pivotal Royal Free Hospital outbreak of ME, far more than 4% of a
previously healthy population of doctors and nurses contracted an unknown
infection at roughly the same time (the hospital had to close due to lack of
staff). This fact would question the role of XMRV as a key predisposing factor
if it only occurs in 4% of the population.
Until we know more about the possible role of XMRV in ME/CFS there is no point
in asking your doctor about antiviral drug treatment. If it turns out that the
virus does play a role in causing or maintaining ME/CFS then antiviral drug
treatment will need to be investigated. This will involve clinical trials to
test possible drug treatments for both safety and efficacy – a process that
normally takes a considerable amount of time and money.
The 2007 NICE Guideline on ME/CFS specifically states that doctors should not
use antiviral medication to treat ME/CFS. This dogmatic position is unlikely to
change without clear evidence of benefit in good quality randomised clinical
trials.
Role of the MEA Ramsay research fund
The ME Association is keen to progress this research in the UK through any way
we can help. We have already made contact with virologists who are interested
in this virus here in the UK and funding from the Ramsay Research Fund
could be made available very quickly if we receive a good quality research
proposal.
Since publication of these results it has become apparent that a number of
international research groups are intending to try and confirm or refute the
findings. The MEA has been contacted in relation to four such groups already –
two from overseas. This is obviously good news and should help to clear up some
of the immediate uncertainties.
If volunteers are required for any research taking place in the UK we will place
an announcement on the MEA website
KEY FACTS ABOUT THE XMRV RESEARCH
An American group from the Whittemore Peterson Institute, in collaboration with
the National Cancer Institute and the Cleveland Clinic, have reported
finding evidence of a human retrovirus known as XMRV in blood samples taken from
people with ME/CFS.
Using peripheral blood mononuclear cells, DNA (viral genetic material) from the
virus was found in 67% of patients (68/101) compared to 3.7% in healthy controls
(8/218). in cell culture in the laboratory, the XMRV virus
was shown to grow
Further studies have found that 95% of people with ME/CFS have antibodies to the
virus, indicating an immune response to a recent or past
infection.
Blood samples were collected from people with what is referred to in the paper
as CFS who live in different parts of the United States, as well as from healthy
controls.
A more detailed, but easy to understand, summary of the XMRV research has been
prepared by Dr Suzanne Vernon for the CFIDS Association of America. This can be
read on their website: www.cfids.org/cfidslink/2009/110402.asp
The paper in Science does not provide any detailed information about the patient
group (ie age, gender, illness characteristics) or control group. However, a
report on the research published in The Wall Street Journal states that 20/101
people in the CFS group also had a lymphoma, a type of cancer affecting the
lymph nodes. Questions have therefore been raised about the inclusion of these
patients in the CFS group, as well as the make up of the control group and how
these patients were selected. See commentary from Professor Andrew Lloyd
published on the website of the ME/CFS of NSW, Australia:
www.me-cfs.org.au/node/448
KEY FACTS ABOUT RETROVIRUSES AND XMRV
·
Retroviruses
are a small group of human viruses that consist of HIV (causing AIDS) , HTLV-1
(causing T-cell leukaemias and lymphomas) and HTLV-2 (often asymptomatic not yet
clearly linked to any specific disease).
·
They were discovered in the 1980s when it became possible to culture T-cells in
vitro.
·
They infect CD4 bearing lymphocytes – a special type of immune system cell that
is derived from the thymus gland.
·
Endogenous retroviruses (ERVs) are also found in humans and usually cause no ill
effects.
·
XMRV
is retrovirus that was first described about three years ago in some men who
have prostate cancer.
·
It may also be linked to other medical conditions, including fibromyalgia.
·
XMRV
is related to a group of viruses that can infect mice.
·
This type of virus is thought to be transmitted through body fluids such as
blood, semen and breast milk. It is not thought to be transmitted through the
air – like a flu virus.
·
Testing for evidence of the XMRV virus in blood is currently only available at a
few specialised laboratories here in the UK.
·
Demonstrating a link between a retrovirus and ME/CFS does not, by itself,
resolve the physical vs psychological debate. Research studies have demonstrated
links between retroviruses and diseases as diverse as autoimmune disorders
(which could be relevant to ME/CFS), immunodeficiency diseases, multiple
sclerosis, tumours, anaemias and schizophrenia.
The bottom line to this interesting research is that it currently raises more
questions than answers.
·
Does the presence of XMRV in healthy people make them more likely to develop
ME/CFS when another infection appears?
·
Does XMRV cause ME/CFS in some cases?
·
Does XMRV become active as a result of having ME/CFS?
·
Or is it simply an innocent bystander with no role in the illness?
·
Should XMRV be treated?
When we have accurate answers to at least some of these questions we can move
forward, if necessary, with testing and treatment.
We will update this summary as further information
becomes available.
Dr Charles Shepherd
Hon Medical Adviser, ME Association
Detection of an infectious retrovirus, XMRV, in blood cells of patients with
chronic fatigue syndrome. Lombardi V et al. Science October 8 2009 Abstract:
http://www.sciencemag.org/cgi/content/abstract/1179052
A new virus for old diseases? Coffin JM and Stoye JP. Science October 8 2009
326; p215 Abstract:
http://www.sciencemag.org/cgi/content/abstract/1181349
Additional online data from the study can be obtained if required.
XMRV has also been found in an American study in men who have prostate cancer.
This was partly why the ME/CFS study was carried out. However, the most recent
study on XMRV in prostate cancer from Germany has queried any such a link and
suggested that one possible reason could be a geographically restricted
incidence of XMRV infections.
Reference:
Lack of evidence for xenotropic murine leukaemia virus-related virus (XMRV) in
German prostate cancer patients. Retrovirology 2009, 6:92. Available on-line:
http://www.retrovirology.com/content/6/1/92
Return to Home Page click HERE Return to Virus Page click HERE