The recent paper published by the NIH/FDA in
USA, which supports the research findings of WPI/NCI/CC was
authored by Harvey Alter et al.
OK, I've read the paper now, and so, in case anyone still has
any confusion relating to the MLV-related viruses that Alter
found... I might be able to bring some clarity to the
situation... or probably not... but I’ll have a go anyway...
Harvey J. Alter, one of the authors of the paper, says that
many viruses which cause a single disease, such as Hep C and
HIV, have multiple variants, or types. He specifically said that
Hep C has a quite a few different variants. So, he is saying
that, what they have found in CFS/ME, is exactly what he would
expect from a human retrovirus.
In the published paper, Alter refers to three different types of
virus that he detected in CFS patient blood samples, and there
was also a fourth type in a blood donor sample.
|There were three different MLV-related retroviral gag gene sequences
identified by PCR in the blood samples of the CFS
patients and a fourth variant was detected in blood
The sequence of all four variants were more closely
related to the sequence of polytropic mouse
endogenous retroviruses (mERV's) than to those of
Alter refers to these virus types specifically as
'CFS Type 1', 'CFS Type 2' and 'CFS Type 3'. It is not clear
what Alter is exactly referring to by these terms (i.e. does he
mean a type of CFS, type of virus or type of gene sequence?),
but it seems that he is at least referring to the "viral gag
gene sequences" that he was detecting.
|Although variations were observed,
the majority (18/21, 86%) of CFS patient samples had
the same viral gag gene sequence (CFS type 1)...
This study strengthens the WPI's work, and it does not weaken it
in any way. It has brought to light a range of new virus types
that are associated with ME/CFS. And it means that these
retroviruses might be found in even more of us than are
currently testing positive for XMRV. At the moment, I think
about half of the members of this forum are testing negative,
and so it might end up that they test positive for these other
variants in the future. I believe that this makes our collective
future even more hopeful.
So, in the case of ME/CFS, Alter seems to be saying that a group
of viruses (or variants of virus) are associated with a single
disease, or syndrome... These viruses are all MLV-related
viruses (murine leukaemia virus - related viruses), and they are
also all Human Gamma Retroviruses (HGRV)... They have a number
of different strains, or varieties, or variants, or types
(whatever you want to call them). In this published paper, all
the variants which were discovered, except the one discovered in
the blood donor, are all shown to be associated with a single
disease, known as ME/CFS, or you could say that they are all
associated with a 'syndrome' (CFS is a syndrome), where the
patients may yet be shown to exhibit different symptoms within
that syndrome, possibly relating to being infected by the
different types of virus. The viruses might also be associated
with other diseases, such as MS, Autism, Gulf War Syndrome, Lyme
Disease... and there is ongoing research looking into all of
these. The possibility of multiple infections, of different
MLV-related viruses, in an individual, might also contribute to
increased, or a wider range of, symptoms.
Alter has very firmly stated that his study complements,
confirms and broadens the WPI's research, and does not detract
from it in any way.
So, it seems that they have discovered Human Gamma Retroviruses
(HGRV's) in people with ME. ('HGRV' seems to be the umbrella
term for these MLV-related human gamma retroviruses). XMRV is
one of these HGRV's, as Judy Mikovits has always said. The Alter
study, and Judy Mikovits, have also confirmed that there are
also different types of XMRV. This paper specifically refers to
"XMRVs" in the plural. There are also diagrams in the paper
showing how the XMRVs relate to the other, new, MLV-related
for a diagram, extracted from the Alter & Lo paper, of
a phylogenetic tree of MLV-related virus gag gene sequences
taken from blood samples of CFS patients and blood donors, and
how they related to MLV's:
All the Human Gamma Retroviruses (HGRV’s) found, so far, are all
MLV-related viruses (MLV = murine leukaemia virus) (Note that
MLV’s are mouse retroviruses that cause cancer in certain types
of mice.) The viruses, that Alter and Mikovits have published
papers on, have all been designated as MLV-related-viruses.
Alter seems to base his findings on virus gene sequences, rather
than whole virus genomes. I suppose that if a mouse virus, or
mouse related virus is found in the human population, then these
newly discovered human viruses need to be designated as human
viruses, rather than mouse viruses.
I'm not sure, from the wording of the paper, how much similarity
there is between the mouse viruses and the human viruses.
i.e. were all of Alter's viruses were previously unknown
viruses, but similar to existing MLV's? or are they identical to
existing MLVs? Have these viruses mutated enough, since being in
the mice population, such that they can be called new viruses?
Alter checked all of his blood samples for contamination with
mouse DNA, which showed negative for all mouse DNA, which
suggests that all these viruses have mutated and are not
identical to any mouse retroviruses, therefore they can be
called new viruses.
HGRV's (specifically MLV-related viruses) have now been found in
a high percentage of ME/CFS patients in two published studies.
(The Science paper, and now the PNAS paper).
XMRV is one type of these MLV-related viruses (and so it's also
an HGRV)... It has now been confirmed that there are different
variants, or types, of XMRV.
Here's what 'XMRV' stands for:
X - Xenotropic
M - Murine Leukaemia Virus (MLV)
R - related
V - retrovirus
So, as you can see from the 'M' (shortened from MLV) in XMRV,
XMRV is related to Murine Leukaemia Viruses (MLV's), just the
same as Alter's viruses are. XMRV was correctly classified as an
MLV-related virus, the same as Alter's viruses. Throughout his
paper, Alter refers to “MLV-related viruses” and “MLV-like
Why Alter's viruses cannot be called 'XMRV':
A 'Xenotropic' virus cannot infect the species of origin (in
this case, mice); it can only infect other species (in this
It is important to note that the HGRVs, or MLV-related viruses,
that Alter found could not be designated as being
'Xenotropic' type, or related to Xenotropic type viruses.
The MLV-related viruses that Alter found most closely relate to
'Polytropic' MLV's, not 'Xenotropic' MLV's.
This means that they cannot be referred to as 'XMRV' because the
'X' (Xenotropic) does not apply to these viruses.
Instead, they are 'polytropic Murine Leukaemia Virus-Related
Viruses' (So, I suppose he could have named them 'PMRV' instead
Alter’s MLV-related viruses are referred to as 'polytropic',
because the MLV's which they related to can infect
both the host species (mice) and another species (humans),
whereas Xenotropic viruses cannot infect the species in
which they originate (i.e. mice), but can infect another species
(Please see notes at the bottom of the page on the meaning of
So, Alter's viruses are polytropic-MLV-related-viruses (the
MLV's they are related to can infect mice), whereas XMRV
is a xenotropic-MLV-related-virus (the MLV's it is related to
cannot infect mice). The only difference in the terminology
is the use of the words 'xenotropic' and 'polytropic', or a 'p'
and an 'x'.
So, we have Alter's new p-MLV-related-viruses and Mikovit's
x-MLV-related-viruses (XMRV). Both of these are 'MLV-related
viruses', and they both fall under the umbrella term 'Human
Gamma Retroviruses' (HGRVs).
There are multiple varieties of both types of viruses. Alter has
found CFS Type 1, CFS Type 2 and CFS Type 3 (although these
terms might relate to gene sequences, rather than the actual
viruses – it’s not clear), and another, fourth type, in a blood
And Alter and Mikovits both seem to be saying that Judy Mikovits
has also found multiple variants of her xenotropic-MLV-related
All of these MLV-related viruses, are HGRV's, so they all fit
under the newly designated name Human Gamma Retrovirus HGRV.
(Or, at least, is has been reported that HGRV is the new
umbrella name for these viruses.)
Amy Dockser Marcus' Wall Street Journal blog says that Judy
Mikovits has found polytropic type MLV-related viruses in some
of the samples in her original Science study (so, along with
XMRV, this means she is finding more than one MLV-related virus
infection in individual samples), and I imagine that she is
working furiously to find out the significance of this.
One other interesting thing to note is that the
'commentary' in PNAS says that:
But in the months since then, they
have continued to study the CFS patients included in
the Science paper and Mikovits says that almost all
of them are positive for one or more MLV-related
viruses, including X and P.
So I believe that whether these new viruses are
related to polytropic or xenotropic MLV's is not clear cut and
is not particularly significant... it's just a case of wording,
and possibly an unfortunate case of using an 'X' in the naming
A note about the meaning of 'Xenotropic':
Note that XMRV itself is an infectious human virus, and
therefore it is not a Xenotropic virus, but the MLV's that it
relates to are Xenotropic.
(zen″o-tro´pik) pertaining to a virus that is found
benignly in cells of one animal species but that
will replicate into complete virus particles only
when it infects cells of a different species.
So this means that a Xenotropic retrovirus is
encoded genetically into the DNA of the original host species
(e.g. a mouse), but the virus is not whole or complete, and
cannot replicate in the host species. It can only infect, and
replicate in, a different species, in which it becomes a whole,
exogenous, infectious virus.
Xenotropic (Science: virology) refers
to a genetically transmitted retrovirus that cannot
replicate in the host species that is harbouring it
but which can infect and can only replicate in the
cells of a different species.
A Xenotropic virus is benign in the original species (i.e. it
does not cause disease). It is not possible to infect, or
re-infect, the original species (i.e. in this case, a mouse)
with a Xenotropic virus because the species has a genetic
resistance to that virus.
So, a Xenotropic virus cannot infect the original host (mouse)
but can only infect another species, in this case humans.
This appears to relate to these MLV's being endogenous
retroviruses in mice. The endogenous virus DNA is part of the
mouse DNA, and it is not a whole, replicating, virus when in the
mouse. It is only when a Xenotropic virus jumps to another
species (e.g. to humans) that it is able to start replicating
and forming whole, or complete, viruses, thus becoming an
infectious exogenous retrovirus.
A Xenotropic virus does not have to have mutated in the
new host species for it to be Xenotropic.
A question that has been raised is, if Xenotropic viruses are,
by definition, 'benign' in the host species, then why are these
MLVs referred to as 'Xenotropic', if MLV's are known to cause
cancer in certain types of mice?
This question is explored in
the discussion after my blog entry:
I don't think that XMRV has been found, genetically, in mice,
which is why it is called an MLV-related virus, and not an MLV.
Alter checked all of his blood samples for contamination with
mouse DNA, which showed negative for all mouse DNA, which
suggests that all these viruses have mutated since being in the
mouse species, and they are not identical to any mouse
retroviruses, so I imagine that the same was done for the XMRV
This means that the origins of XMRV are a mouse virus, but that
it has mutated in the human population (or before it reached the
human population if another species was also involved), such
that it is no longer an MLV.
XMRV has 'Xenotropic' in its name because it is closely related
to a Xenotropic mouse virus, not because it is actually a
Xenotropic virus. It is an exogenous human retrovirus, not a
So, XMRV has its origins in mice, and it has mutated in humans
enough so that the XMRV virus DNA cannot be found in mouse DNA.
I imagine that mice still have a resistance to it and so cannot
be infected with it, but I'm not clear about this. If the virus
mutated enough, then mice could lose their resistance to it.
XMRV DNA is not found in mice and therefore it is not actually a
Xenotropic mouse virus (and it's not a Xenotropic human virus)
but it is a (Xenotropic mouse virus)-related virus, and a human
retrovirus, which is exactly how it has been designated.
I do have a question that doesn't seem to be answered... If we
know that polytropic and xenotropic mouse retroviruses exist,
then why haven't there been more studies done on these viruses
before? Polytropic and Xenotropic viruses, by definition, can
infect other species (i.e. humans), so why have these MLVs only
been investigated recently? Or have we only just discovered that
there are Xenotropic and Polytropic MLV's?
Submitted to Invest in ME by Bob Courtney - August 2010