Het tij lijkt (weer) te keren als het gaat om de rol van XMRV/MLV.
In navolging van De Wall Street Journal lijkt nu ook het veel gelezen De New York Times
zich kritisch en objektief met de zaak te gaan bemoeien (zie onderstaand artikel).
Vincent Racaniello licht in de Virology Blog kort de integratie van XMRV in het DNA toe.
Integratie in het DNA van de gastheer is de derde stap in de levenscyclus van een retrovirus.
Het feit dat XMRV zich in het DNA nestelt (een provirus) weerspreekt de "vervuilingstheorie".
Tenslotte legt het Whittemore-Peterson Instituut, bij monde van Annette Whittemore,
in een openbare verklaring opnieuw uit waarom XMRV een virus en geen "laboratoriumvervuiling" is.
Retroviral integration and the XMRV provirus
By Vincent Racaniello
4 January 2011
A strong argument that the novel human retrovirus XMRV is not a laboratory contaminant is the finding that
viral DNA is integrated in chromosomal DNA of prostate tumors.
Why does this result constitute such strong proof of viral infection?
Establishment of an integrated copy of the viral genome – the provirus – is a critical step in the life cycle of retroviruses.
Proviral DNA is transcribed by cellular RNA polymerase II to produce the viral RNA genome and the mRNAs required to complete the replication cycle.
Without proviral DNA, retroviral replication cannot proceed.
The isolation of the entire proviral DNA, including both flanking integration sites,
from patients with prostate cancer or chronic fatigue syndrome would be additional evidence that XMRV is a virus that infects humans.
Exhausted by Illness, and Doubts
January 3, 2011
"Our conclusion is quite simple: XMRV is not the cause of chronic fatigue syndrome,"
said the senior author of one of the studies, Greg Towers, a professor of virology at University College London,
in a statement released by Wellcome Trust Sanger Institute, the British research center that co-sponsored it.
In a statement responding to the new papers in Retrovirology,
Judy A. Mikovits, director of research at Whittemore Peterson and the senior author of the Science study, said
her team took extensive steps to rule out P.C.R. contamination and
also focused on other approaches to finding XMRV.
"Nothing that has been published to date refutes our data," she said.
A Human Retrovirus with Unknown Pathogenic Potential, Not a Lab Contaminant
January 4, 2011.
The recent proclamation that XMRV is not the cause of CFS,
came from an individual who did laboratory experiments to show how PCR experiments can become contaminated.
These results have nothing to do with the reality of a disease
or the methods used by those who have detected XMRV in the blood and tissue of patients found to be infected.
The positive studies, which cannot be explained away by PCR experiments,
are those which have used multiple methods to show that
XMRV is a live replicating gamma retrovirus in human blood and tissue samples
using the gold standard methods of viral isolation and antibody testing, in addition to PCR.
Unsupported conclusions, such as the one offered by the Wellcome Trust spokesman,
often create sensational headlines but do little to move science forward.
Authors of the positive XMRV studies have been extremely careful not to claim causality,
realizing that more scientific research is required to make such a statement.
However, one fact still remains clear.
Not one of the negative studies changes the results of
the scientific research done by Lombardi et al., Lo et al., Urisman et al., and Schlaberg et al.
The WPI-led scientific study, which rigorously ruled out contamination,
revealed high associa-tions of gamma retroviruses with physician-diagnosed CFS patients,
using four different methods of detection.
Recent commentary associated with the negative research papers on XMRV, which used only one testing method,
claimed that these studies proved that XMRV was not the cause of human disease.
On the contrary, what the authors of the contamination studies confirmed
is something that most experienced scientists already know;
there are risks associated with using PCR if one does not properly control for contamination.
They cannot conclude that other research groups had the same problems or that XMRV is not the cause of CFS.
Most significantly, the recent Retrovirology publications
failed to address the most important pieces of scientific evidence
of human infection in the previous XMRV studies, including the fact that
XMRV positive patients produce human antibodies to gamma retroviruses,
XMRV integrates into human tissues,
and infectious virus has been cultured from the blood of hundreds of patients
with a diagnosis of Chronic Fatigue Syndrome and M.E.
Humans do not make antibody responses to mouse DNA sequences from contaminated lab experiments.
The Retrovirology studies only point out that XMRV research
cannot be done in a mouse laboratory without extreme caution and
should not rely solely on PCR methods.
Many researchers realize that
the question of gamma retroviruses and human disease
cannot and should not be dismissed lightly.
Retroviruses integrate into their hosts DNA causing life-long infection.
Human retroviruses, such as HIV and HTLV-1,
are causative for immune deficiencies, neurological disease and cancer.
Animal studies involving XMRV
demonstrate that the virus moves quickly away from the blood
to various organs within the body, such as the spleen, lymph nodes, GI tract, and reproductive organs.
This helps to explain why the virus is difficult to detect in blood
even as it replicates in the tissues of those infected.
Other studies using mouse models of Murine Leukemia Virus infection,
a close relative of XMRV, have shown
significant tissue involvement soon after infection,
resulting in many physical symptoms of disease
including cognitive deficits and immune deficiencies,
symptoms which are well documented in patients with XMRV associated diseases.
Many anxious patients have asked,
Where do we go from here? and Is this the end of XMRV research?
The answer to the second question is an unequivocal no.
As to the first question,
a quick check of the status of ongoing research in various labs
confirms that the research groups who have been working on XMRV over the past year
are still hard at work developing better assays
to check the worlds blood supply for the new retrovirus,
finding correlates of immune dysfunction,
engaging in animal studies,
extending their findings to other groups of patients,
and in general, enthusiastically continuing their research.
They understand that novel scientific discoveries,
which threaten current dogma,
will continue to be challenged until the evidence can no longer be denied.
For instance, there are still those few who question the fact that HIV is the cause of AIDS.
It took Nobel Prize winner, Dr. Barry Marshall, 17 years and
three trials in which he infected and
then cured himself of H-Pylori associated ulcers,
before the medical world would accept the fact that the bacterium causes the disease.
Today we are engaged in a new battle
to prove that human gamma retroviral infections, such as XMRV,
are underlying pathogens in neuro-immune diseases and untold cancers.
It is clear that more research must be done
to clarify the role of gamma retroviruses in human disease.
However, when a pathogen such as XMRV
is found in over 80% of those tested with the same diagnosis,
causality is clearly a reasonable hypothesis
that begs further scientific and medical research.
It is a known fact that important questions of causality
can often be answered through well designed clinical trials.
For those who have suffered for years from these debilitating diseases,
novel drug trials cannot begin soon enough.
WPIs collaborative research projects are revealing the
infectious and inflammatory nature of neuro-immune diseases, providing
strong evidence against the use of CBT and exercise therapy as rational treatments
for those who are ill.
Such knowledge underscores the urgent need for
much more private and federal funding of biological research to
provide diagnostic tests and effective drug therapies for the millions who are ill,
stop the spread of infectious retrovirus(es), and
end the devastating cycle of disease.
President Whittemore Peterson Institute
Met dank aan Erik en Evelien.