Xenotropic MLV's can infect many mammals and also (wild) mice

[Jemal]

I just found this article from a NIH researcher that will appear in Retrovirology. I think it is new and it contains some interesting information:

The mouse xenotropic MLVs (X-MLVs) were originally defined by their inability to infect cells of their natural mouse hosts. It is now clear, however, that X-MLVs actually have the broadest host range of the MLVs.

Nearly all nonrodent mammals are susceptible to X-MLVs, and all species of wild mice and several common strains of laboratory mice are X-MLV susceptible. The polytropic MLVs, named for their apparent broad host range, show a more limited host range than the X-MLVs in that they fail to infect cells of many mouse species as well as many nonrodent mammals.

http://7thspace.com/headlines/36542...ammaretroviruses_and_their_xpr1_receptor.html

The plot thickens?

 

[Enid]

Thanks for posting Jemal - hope all these findings can come together.

 

[CBS]

Here is a link to the abstract in Retrovirology: http://www.retrovirology.com/content/7/1/101

There is a link on this page to the entire article (pdf).

 

[Jemal]

Thanks for the additional link CBS!

It's pretty significant I think...

edit: there's a whole lot of new info on XMRV in that article, pages of it!

The XMRV virus and X/P-MLV sequences found in humans may have been acquired directly from mice, or after transmission from mice to another species in contact with humans. If there is direct transmission from infected mice, this could be reflected in the geographic distribution of virus and/or receptor type in mice and the worldwide incidence of prostate cancer. Studies have reported very different rates of XMRV detection in prostate cancer patients (reviewed in [122]), and while these differences may have technical explanations, it is also possible that some of these differences are due to geographic differences in exposure to XMRV. The highest rates of prostate cancer are found in the U.S. and lowest rates are found in Asian countries like Japan, India and China [123]. Rates in Europe are lowest in Eastern European countries. This distribution generally corresponds to the distribution of Xpr1 receptor variants in mouse populations; the most permissive allele, Xpr1sxv, is found in high tumor incidence areas, and the most restrictive allele, Xpr1m, is found in low tumor 20 areas like Japan and eastern Europe. Mice in low tumor areas of Asia also carry receptor blocking genes [124] further indicating that these mice might be poor candidates for zoonotic transmission to humans. While these observations are suggestive of direct transmission between mice and man, it should also be noted that mice in areas of high tumor incidence are not known to carry infectious X/P-MLVs or expressed MLV ERVs.

I don't understand all of it though :headache:

I like the conclusion.

The worldwide distribution of mice that carry MLVs and the broad host range of the X-MLVs suggest that we are only beginning to describe what may be common and widespread interspecies transmissions.

It's from a NIH researcher I think? So that's good news as well...

I am telling you, times are changing, I can just feel it. This is something big.

 

[redo]

If it can infect wild mice, chances are good it can get transferred from mice to humans via ticks...

 

[Jemal]

If it can infect wild mice, chances are good it can get transferred from mice to humans via ticks...

Yeah, it looks like a possible infection route. It could also explain why some people with Lyme don't do well on antibiotics, they could have gotten infected with both Lyme and this virus.

 

[Jemal]

Now that we have the full article we should probably move this thread to the XMRV research subforum. If a mod could do this... thanks.

 

[alex3619]

Vets needed

Hi everone,

Wow, confirmation of some ideas that are discussed on PR from time to time.

Mammals: try dogs, cats, rodents (not all of them though), cows, pigs, sheep, goats, horses, donkeys, bats etcetera.

Cross-species transfer can be broader than just ticks. Rodents frequently infest grain stores. Ever eat wheat, rice, oats etcetera? They can also infest animal feed. Ever eat beef, drink milk, eat cheese? Now the infectivity from these is going to be low due to cooking and pasteurization of milk and culturing of cheese, but people do eat blue steaks, and in many parts of the world it is still legal to drink raw milk. As for grains, I once bought a bag of rice that seemed to have had a rat party at some point (say no more). It happens. How many of us have cats, dogs, or more exotic pets? How many did we have as a child?

In Australia, large regions of the country have fruit bats, which can travel very long distances.

All of this doesn't prove anything except this: we need to cast a much wider net, and we need to get veterinary researchers on board with this as well. Lets rule everything out - and in the process maybe some serendipity may come our way and we discover something important.

Bye
Alex

 

[Merry]

Thanks so much, Jemal.

I've been wondering if XMRV could infect other mammals. I've thought for a long time I made my dog sick. Later, maybe, a cat.

I've also wondered about the unpasturized milk my maternal grandparents served at their farm. Also I grew up in a house that was badly infested with mice.

Like Alex, I've wished veterinarians would join in the research and discussion.

 

[X-Man]

I've been wondering if XMRV could infect other mammals. I've thought for a long time I made my dog sick. Later, maybe, a cat.

I too have wondered if I made a previous dog of mine sick. I am XMRV+. A few years ago I had to put down my black lab, who was about 10 years old. It may have been old age, but he went downhill fast in about a six month period. It was like he had ME. His personality changed. He was easy going before his crash then he became very timid and more agressive. He also had problems walking and moving around and going up stairs. He also became incontinent & started drinking his own pee, prefering it to water. Even before I learned about XMRV, I wondered if I had given this to him. I thought I may have given it to him through my saliva: I would give him food that I had eaten off of like pizza crusts or fat from steak. But as I said, maybe it was just his older age.

 

[omerbasket]

Thanks for the additional link CBS!

It's pretty significant I think...

edit: there's a whole lot of new info on XMRV in that article, pages of it!



I don't understand all of it though :headache:

I like the conclusion.



It's from a NIH researcher I think? So that's good news as well...

I am telling you, times are changing, I can just feel it. This is something big.

I think that the big quote you brought here is nonsense. Theoretically, it could be, but this really doesn't seem like a geographic thing. First of all - the CDC's team which found nothing in their CFS XMRV study, tested the 20 XMRV-positive samples that were sent to them by the WPI, and found non of them to be positive. So here we know that it's not a geographic thing, but a difference in techniques - I believe it is the CDC's technique which is useless - the CDC would probably think something else. Then, we have the fact that WPI's "Science" study tested people from 12 states in the USA (I think) and also people from abroad - and they found 98% of them to be positive. Now, they said: "perhaps it's not in europe", because studies done in Britain, Holland and Germany didn't find XMRV. But when WPI tested patients from Britain, they found at least 60% of them to be positive for XMRV. And Dr. De-Merleir also found XMRV positives in Belgium and other countries in europe. And the German respiratory tract study also found XMRV. And Dr. Chenney found XMRV in very high percentage of his patients, and The NIH/FDA found MLV-related viruses in 86.5% of the patients and 6.8% of the controls. And we know that patients in Norway are testing positive for XMRV too, and we know of other patients from around the world testing positive for XMRV. And you know what? Even in Japan 1.7% of healthy people were found to be positive for XMRV. And that's without mentioning the prostate cancer studies.

So yes, unless you haven't proven by a 100% that something is not true, it's possible that it is true. But the likelyhood of that idea seems very very small to me, and this is really not the theory that should be pursued right now.

 

[Jemal]

I don't believe it's a geographic thing either Omerbasket. The big thing here is that these X-MLV's are able to infect all kinds of mammals and even mice. It could be that other mammals are spreading the viruses, probably even humans themselves. So the virus may have been limited to certain mice in certain areas at one time, but I think it has spread globally. I don't think this study shuts the door on that option, on the contrary: I think it creates many new possibilities.

 

[George]

I think that the big quote you brought here is nonsense. Theoretically, it could be, but this really doesn't seem like a geographic thing. First of all - the CDC's team which found nothing in their CFS XMRV study, tested the 20 XMRV-positive samples that were sent to them by the WPI, and found non of them to be positive. So here we know that it's not a geographic thing, but a difference in techniques - I believe it is the CDC's technique which is useless - the CDC would probably think something else. Then, we have the fact that WPI's "Science" study tested people from 12 states in the USA (I think) and also people from abroad - and they found 98% of them to be positive. Now, they said: "perhaps it's not in europe", because studies done in Britain, Holland and Germany didn't find XMRV. But when WPI tested patients from Britain, they found at least 60% of them to be positive for XMRV. And Dr. De-Merleir also found XMRV positives in Belgium and other countries in europe. And the German respiratory tract study also found XMRV. And Dr. Chenney found XMRV in very high percentage of his patients, and The NIH/FDA found MLV-related viruses in 86.5% of the patients and 6.8% of the controls. And we know that patients in Norway are testing positive for XMRV too, and we know of other patients from around the world testing positive for XMRV. And you know what? Even in Japan 1.7% of healthy people were found to be positive for XMRV. And that's without mentioning the prostate cancer studies.

So yes, unless you haven't proven by a 100% that something is not true, it's possible that it is true. But the likelyhood of that idea seems very very small to me, and this is really not the theory that should be pursued right now.

Omer, Jemal didn't say that, The article puts that in as a possibility. Now if you want to tell Christine A Kozak of the NIAID at the NIH that she's wrong then you can reach her at ckozak@niaid.nih.gov and her profile is here at http://www.niaid.nih.gov/labsandresources/labs/aboutlabs/lmm/viralbiologysection/Pages/kozak.aspx go for it! (grins)

In addition she writes the following that is in line with current thinking,

However,
M. domesticus mice trapped at various sites throughout its western European range and
in the Americas all carry Xpr1sxv (Figure 6). It is thus possible that Xpr1n arose later, in
the fancy mouse progenitors of laboratory mice. These fancy mouse interspecific
hybrids would have acquired M/Pmvs from domesticus and Xmvs from musculus and
castaneus, and a restrictive receptor might have provided a survival advantage for
these mice.

 

[George]

The transmission of XMRV to humans was likely accompanied by adaptive
changes, and the observed sequence and phenotypic differences of XMRV relative to
the X/P-MLVs have focused particular attention on the glycogag leader region, LTR and
env. XMRV carries unusual deletions in glycogag, a region that in E-MLV influences
virus release and sensitivity to interferon [125] and also inhibits the activity of the host
cell antiretroviral factor APOBEC3

Two interesting tidbits I thought. First there is a lot of information about the cross overs in the P and X MLV's. More or less XMRV is P/X variants of the original endogenous P/X-MLV's. So in effect she is saying Lo and Alter found XMRV and WPI found P/X-MLV's since in this case XMRV is the collimation of that family tree. Pretty cool that's on pages 20 and 21.

This part I thought was interesting because of the interferon which may be why a synthetic interferon works when regular interferon doesn't and the part about XMRV inhibiting the APOBEC3 antiviral pathway. Now I've seen a couple of papers that say that APOBEC3 inhibits XMRV but this is the first I seen that XMRV inhibits APOBEC3 which makes me wonder if I either read the earlier Bishop papers incorrectly or if there are other papers out there floating around that haven't made the publishers yet.

 

[pictureofhealth]

Hi everone,

.. we need to cast a much wider net, and we need to get veterinary researchers on board with this as well. Lets rule everything out - and in the process maybe some serendipity may come our way and we discover something important.

Bye
Alex

Agree - great idea to get some vets on board with this. They may already have a lot of information about it.

A vet local to me in the UK was diagnosed with ME/CFS many years back. He saw a lot of simliar symptoms in horses too and studied and wrote about this. When his health improved he travelled and lectured about it.

Sadly can't remember his name (of course) - David ... yes, 'David in the UK', that narrows the search right down doesn't it??!! Will post more info if I find it and remember his name.

 

[pictureofhealth]

Equine CFS:

Here is an article describing successful treatment of 4 horses diagnosed with CFS, using an arsenic type compound - thiacetarsamide sodium.

This has been posted on a well known CFS board.

http://www.cfsresearch.org/cfs/tarello/chronic-fatigue-syndrome-horses.htm

The Abstract suggests it is an English study, but I think the horses were in Italy (?!)

Anyway, the results suggest a bacterial infection, so is it the same illness? Household pets are also mentioned.

Also of note: Quote: " It has been suggested [27] that CFS outbreaks such as those that occured in Incline Village, may result from the acquisition of low-grade toxic Staphylococcus which in turn may facilitate the reactivation of HHV-6 and other herpesviruses [27]"

Perhaps we can now substitute Staphylococcus with MLV's, XMRV?

 

[Mark]

This does look like an important piece in the puzzle, it's nice to have some worthwhile new science to chew over, feels like it's been a while...(Dr Singh's patent stuff was good but not published yet and thin on the detail...).

A bunch of interesting possibilities open up. I must admit, I was going straight for that whole geographic explanation thing until omerbasket pointed out that it doesn't appear to fit the facts of XMRV testing at all. I was reminded of the "iron curtain" across Europe for two broad subtypes of mice genetics (do I remember right?) as mentioned at the 1st International XMRV Workshop.

Even though it looks like that geographic thing doesn't quite work, I'm still wondering if it might still play a part. All the PCR testing is only looking for particular sequences which are considered characteristic for XMRV, so if the WPI's tests were all looking at sequences that are preserved across various P and X MLV's they could pick up various different sub-types. Indeed, remember the WPI have refined their testing and increased the positives found since the Lombardi study, so they may well now be picking up more of the P-MLV variants that Lo/Alter found as well, and calling them all "XMRV". Pretty much all the positive evidence that omerbasket is talking about comes from the WPI ultimately of course. And for the rest, well one would have to go right down to the detail of the primer sets used etc in order to answer whether all the results omerbasket lists can be consistent with a geographical variance theory.

The fact of CDC failing to detect WPI positive samples does show that geographical variance can't possibly be the whole story though - there have to be a few dodgy tests in there as well. But the CDC's, of course, was "designed not to detect" Failures by CDC and McClure can easily be added to the theory of geographical variance I would have thought. I wonder how it would all stack up with the prostate cancer studies by geographical variance. I suspect there's no way to be sure just based on a crude analysis: you would have to go right down to the detail of everything, primer sets, exactly where samples were actually drawn from, genetic sequences of all the different strains, where the relevant mice live, everything. Maybe that's what they're all feverishly crunching on behind the scenes...

It would be funny if it turned out that the virus can't swim after all...

But I'll forget about that if George assures me I can rule out that line of thinking...

Two interesting tidbits I thought. First there is a lot of information about the cross overs in the P and X MLV's. More or less XMRV is P/X variants of the original endogenous P/X-MLV's. So in effect she is saying Lo and Alter found XMRV and WPI found P/X-MLV's since in this case XMRV is the collimation of that family tree. Pretty cool that's on pages 20 and 21.

Firstly, I just have to ask if all this stuff supports my comments a couple of months ago that the "P-MLVs" might turn out to be "X" and "XMRV" might turn out to be "P", because as novel viruses and with lots of mice species out there, until you've tried infecting them all you don't actually know whether they really are P or X. That seems almost like what I'm reading here. If it is, I'll just throw in a little "told you so" and move on...

Second...George your comment here about the cross-overs seems to say that this might resolve the dispute over whether Lo/Alter really was a confirmation of WPI. Is it possible that the information in this paper clarifies that Lo/Alter really was a true independent verification of WPI, and that the apparent difference between the sequences detected is now explained? If there is now enough detail in this info to say that, then perhaps we now have our independent confirmation?!

This part I thought was interesting because of the interferon which may be why a synthetic interferon works when regular interferon doesn't and the part about XMRV inhibiting the APOBEC3 antiviral pathway. Now I've seen a couple of papers that say that APOBEC3 inhibits XMRV but this is the first I seen that XMRV inhibits APOBEC3 which makes me wonder if I either read the earlier Bishop papers incorrectly or if there are other papers out there floating around that haven't made the publishers yet.

My recollection was that APOBEC3 inhibits XMRV but that later work suggested it wasn't doing so in practice in one PC study. I may have got that wrong; the second set of info again made the picture look more complicated.

If they both inhibit each other, which appears to be pretty clear, then are we looking at a kind of front line in the war here?

The infection of many different species is clearly very significant though, and of course it does fit well with so much that we've talked about in the past. I note that cats are pretty susceptible...again, just as I thought...

Contamination theories are looking a bit thin these days eh?

 

[urbantravels]

It's worth pointing out that there are plenty of viruses that infect animals but don't make the animal sick at all, but cause disease when they jump to another species.

There's no need to look for mice, cats, horses, or whatever with CFS that's just like the human disease; it's in fact more likely that the reservoir species don't get ill - or get ill differently than we do.

 

[George]

The answer to the question is yes. Christine spends the first 18 pages following the phylogenetic tree of the XMRV virus which while it has been named XMRV is a group of specif virus's that have characteristics of both P-MLV's bearing the XPR1 receptor of a specific type as well as X-MLV's bearing the XPR1 receptor of the n type but not being either thus making it a "novel" retrovirus which can not be describe as purely human since it can infect other mammals as well. Short version XMRV= PMLV+XMLV or P and X got together had a hot and heavy night about 80 years ago and produced a hybrid called XMRV. Either way you slice it this paper reads that XMRV is a hybrid of the P's and X's.

I guess this paper would have bearing on the naming of the virus as well since it is not specific to humans naming it HGRV isn't actually accurate. So who knows maybe we'll get to keep the X factor. (grins)

I think the smoke and mirrors period may be over since I just got this tidbit in the e-mail

Pathogens in the Blood Supply

Tuesday, March 29, 2011 | 1:00 PM - 5:00 PM
The New York Academy of Sciences

Presented by the Emerging Infectious Diseases & Microbiology Discussion Group

According to the American Blood Center, approximately 14 million units of blood are transfused in the United States every year. Current screening protocols routinely test for several pathogens, including the Hepatitis B virus, Hepatitis C virus, Human Immunodeficiency viruses, Types 1 and 2, Human T-Lymphotropic virus Types 1 and 2 and syphilis. Recent headlines indicate that the blood supply may contain other organisms, such as Xenotropic Murine Leukemia Virus Related Virus (XMRV), that are not currently being identified in these routine screens. This symposium will diagnose the current problems, reveal recent advances in the testing and screening of the blood supply, and will explore future directions.
Organizers
Lorrence H. Green, PhD

Westbury Diagnostics
Jennifer Henry, PhD

The New York Academy of Sciences
Speakers
W. Ian Lipkin, MD

Columbia University
Judy A. Mikovits, PhD

Whittemore Peterson Institute for Neuro-Immune Disease
Gail Moskowitz, MD

Healthcare Consultant

Networking reception to follow.

So Ian and Judy are getting together to give a little talk. (eyebrow wiggles) Since Dr. Lipkin has been billed as the Super Hero of Science does that make Judy Wonder Woman to his Batman! (grins)

 

[urbantravels]

I just saw the announcement for that talk float by me in my Facebook news feed and thought, DAMN.

The fact that that talk is scheduled, with that title, with those speakers, well....that suggests things to me.