• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

New research on XMRV in lab mice

fred

The game is afoot
Messages
400
Common inbred strains of the laboratory mouse that are susceptible to infection by mouse xenotropic gammaretroviruses and the human derived XMRV

J. Virol. doi:10.1128/JVI.01863-10
Copyright (c) 2010, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Surendranath Baliji, Qingping Liu, and Christine A. Kozak*

Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases Bethesda, MD 20892

* To whom correspondence should be addressed. Email: ckozak@niaid.nih.gov.

http://jvi.asm.org/cgi/content/abstract/JVI.01863-10v1

Laboratory mouse strains carry endogenous copies of the xenotropic leukemia viruses (X-MLVs), named for their inability to infect cells of the laboratory mouse. This resistance to exogenous infection is due to a nonpermissive variant of the XPR1 gammaretrovirus receptor, a resistance that also limits in vivo expression of germline X-MLV proviruses capable of producing infectious virus. Because laboratory mice vary widely in their proviral content and in virus expression pattern, we screened inbred strains for sequence and functional variants of the XPR1 receptor. We also typed inbred strains and wild mouse species for an endogenous provirus, Bxv1, that is capable of producing infectious X-MLV and that also contributes to the generation of pathogenic recombinant MLVs. We identified the active Bxv1 provirus in many common inbred strains and in some Japanese M. molossinus mice, but in none of the other wild mouse species that carry X-MLVs. Our screening for Xpr1 variants identified the permissive Xpr1sxv allele in 7 strains of laboratory mice including a Bxv1 positive strain, F/St, which is characterized by lifelong X-MLV viremia. Cells from three strains carrying Xpr1sxv, SWR, SJL and SIM.R, were shown to be infectible by X-MLV and XMRV; these strains carry different alleles at Fv1 and vary in their sensitivity to specific X/P-MLV isolates and XMRV. Several strains with Xpr1sxv lack the active Bxv1 provirus or other endogenous X-MLVs and may provide a useful model system to evaluate the in vivo spread of these gammaretroviruses and their disease potential in their natural host.
 

Dr. Yes

Shame on You
Messages
868
Hey Fred!

Interestingly, this study found XMLV (and XMRV) permissive Xpr1 receptor alleles in several lab mouse strains. In the previous paper by these authors (Yan et al 2010), they had assumed that lab mouse strains only had the non-permissive Xpr1n variant. In that paper they were actually surprised to find that none of the house mouse species from which lab mice are descended contained that variant, and that M. domesticus, which has contributed the most to the lab mouse genome, had the highly permissive Xpr1sxv variant.

Will have to check out the full text when I'm up to it.
 
Messages
5,238
Location
Sofa, UK
Well ain't that a thing? I won't pretend I hate to say I told you so...

If my previous post on this subject was horrifically confusing - and it was, sorry - let's sum it up: this research (unless I misunderstand) shows that XMRV is actually Polytropic, at least as far as these mouse species are concerned! As I also pointed out then, the PMRVs that Alter/Lo identified, being partial sequenes, have unknown behaviour: who is to say then that they aren't actually Xenotropic to mice?

So if the XMRVs are actually P, and the PMRVs are actually X, how significant is it, really, that the identification of these retroviruses by the WPI and by the FDA/NIH differs in nomenclature? So they seem somewhat separated on the phylogenetic tree: so what? With what's emerging about horizontal gene transfer these days, that tree could be nonsense anyway. All that matters is: they are novel, they are infectious, they are retroviruses, they are in us, and we need to know what they are and what they do. ASAP!
 
Messages
5,238
Location
Sofa, UK
They were actually surprised to find that none of the house mouse species from which lab mice are descended contained that variant, and that M. domesticus, which has contributed the most to the lab mouse genome, had the highly permissive Xpr1sxv variant.

ETA: Whoops: I think I may be getting confused over which mice are XMRV-susceptible now...so I've rewritten this post...

XMRV can be expected to be present in M.domesticus and in the derived laboratory mice?

And we know that XMRV can infect humans as well, and rhesus macaques as an efficient spreading infection, right?

So does this make contamination theories more or less likely? I would think it makes it most likely that it's perfectly feasible for XMRV to regularly pass back and forth between mice and humans, but I guess it can also be argued that the labs that find XMRV have these variants of mice as a source of contamination (and running all over the CFS and PC samples but not the control samples for some reason...yeah, right...but they will say it...).

Next questions: where do the wild mice with these permissive receptor alleles tend to live? do these findings suggest that laboratory mice have aided the spread of XMRV? and can (P)XMRV infect (some species of) cats as well as mice, humans and monkeys?...
 

anciendaze

Senior Member
Messages
1,841
...Next questions: where do the wild mice with these permissive receptor alleles tend to live? and can (P)XMRV infect (some species of) cats as well as mice, humans and monkeys?...
From one pattern of outbreaks in the 1950s, I tend to believe the wild rodents in question live in the tropics, while many vulnerable people come from high latitudes. The outbreaks often take place when these come together. (This is a SWAG, scientific wild-ass guess.)

If I had money to bet, I would say it can infect cats. Most cats may be safe, but far too many domestic cats are infected with FeLV or FIV. So far, we have seen nothing to indicate infection by one variant of MLV precludes infection by others, and significant evidence to the contrary.
 
Messages
5,238
Location
Sofa, UK
I'd put money on cats too anciendaze. There's a fairly old study that found that practically all PWC had lived with a domestic cat at some point. A large majority of the general population had too, so the finding wasn't seen as massively significant, but it was a big enough statistical difference to be fairly widely reported. I'm a bit surprised I haven't seen that one dug out a bit more often, actually.

If the cat theory pans out, some of my family are going to have a bit of extra apologising to do...I really will be shouting I told you so in that case...the cat in question died of an unexplained total system breakdown with FLV-like properties recently, and it was put down to "just old age"...nothing I could have said could have got anti-FLV-type meds to the poor thing, it was pretty heartbreaking to watch...
 
Messages
5,238
Location
Sofa, UK
This one also could turn out to be interesting to mention in future if it is transmitted by cats: a group of psychs only last year suggesting that cats might provide PWC with "a valuable, and currently underutilized, role in promoting well-being". On the assumption that everything psychs say about us is wrong and damaging, that counts as evidence that cats are involved...:D

http://www.ncbi.nlm.nih.gov/pubmed/19388863
 
Messages
5,238
Location
Sofa, UK
Sorry, this is all horribly off-topic, this thread is supposed to about mice! :D - but I've just got obsessed with looking up the cat research. Can't find that reference that I referred to earlier that suggested most of us had lived with a cat at some point, if anyone has anything on that I'd be most interested. But I found these 3 which are fairly interesting...the rest of the literature is stuffed with psychs exploring whether cats and dogs promote well-being :rolleyes:

Immunological anomalies and thrombocytopenia in 117 dogs and cats diagnosed with chronic fatigue syndrome (CFS).

http://www.ncbi.nlm.nih.gov/pubmed/12688127

Chronic Fatigue Syndrome (CFS) in 15 dogs and cats with specific biochemical and microbiological anomalies.

http://www.ncbi.nlm.nih.gov/pubmed/11440190

Acute encephalopathy induced in cats with a stealth virus isolated from a patient with chronic fatigue syndrome.

http://www.ncbi.nlm.nih.gov/pubmed/8821627
 

free at last

Senior Member
Messages
697
If you guys say its possible,ill buy it, as i had 4 cats with a litter tray around the time my flu type illnesses started with fevers, that eventually lead to a diagnosis of ME. I asked ths question yonks ago on here, but was told no its not possible. Always wondered about those cats ????
 
Messages
5,238
Location
Sofa, UK
I asked ths question yonks ago on here, but was told no its not possible.
I vaguely recall an argument suggesting it was unlikely, but I can't think of any reason why it's not possible. We just know so little about it at the moment that I can't see how the possibility could be ruled out.
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
Straying off-topic for just a little longer.

From co-cure :


"While anecdotal reports have often linked domestic animals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), no formal scientific studies have been reported in the literature. In a recent study, Glass described the interaction between criteria diagnosed ME/CFS patients and their animals. In this study, ME/CFS patients had a significantly higher contact with animals than reported by the American Veterinary Medical Association (MEICFS = 96.8% contact/National Average = 57.9% contact) (4). This study also found that the number of dogs and cats owned by both male and female ME/CFS patients was significantly higher than reported by the American Veterinary Medical Association (Dogs: ME/CFS males = 9.5; ME/CFS females = 7.9; National Average = 1.52) (Cats: ME/CFS males = 6.1; ME/CFS females = 8.7; National Average = 1.95). Finally, this study found that 83% of the animals of ME/CFS patients showed signs which mimicked ME/CFS in humans. Ninety-four percent of these ME/CFS patients had either been the primary caregiver for the sick animals or had intimate contact (sleeping with, being bitten or scratched by, or kissing the animal)."

http://www.co-cure.org/infor14.htm
 

pictureofhealth

XMRV - L'Agent du Jour
Messages
534
Location
Europe
Sorry, this is all horribly off-topic, this thread is supposed to about mice! :D - but I've just got obsessed with looking up the cat research.

Acute encephalopathy induced in cats with a stealth virus isolated from a patient with chronic fatigue syndrome.[/SIZE]
http://www.ncbi.nlm.nih.gov/pubmed/8821627

Mark this third one is from 1995! I wonder if any other researcher ever followed up on it, or if the authors would be interested in a follow up themselves, now that XMRV is being discussed, researched so enthusiastically.
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
...this research (unless I misunderstand) shows that XMRV is actually Polytropic, at least as far as these mouse species are concerned! As I also pointed out then, the PMRVs that Alter/Lo identified, being partial sequenes, have unknown behaviour: who is to say then that they aren't actually Xenotropic to mice?

So if the XMRVs are actually P, and the PMRVs are actually X, how significant is it, really, that the identification of these retroviruses by the WPI and by the FDA/NIH differs in nomenclature? So they seem somewhat separated on the phylogenetic tree: so what? With what's emerging about horizontal gene transfer these days, that tree could be nonsense anyway. All that matters is: they are novel, they are infectious, they are retroviruses, they are in us, and we need to know what they are and what they do. ASAP!

Yes, I agree with that Mark... and remember that XMRV has 'P'-MLV gene sequences in it anyway (it doesn't just have X-MLV gene sequences)... So I'm not sure how the scientists came to the conclusion that XMRV should be classified as an 'X' and not a 'P'. "HMRV" is a much better name for these virus variants.

...
XMRV can be expected to be present in M.domesticus and in the derived laboratory mice?

And we know that XMRV can infect humans as well, and rhesus macaques as an efficient spreading infection, right?

So does this make contamination theories more or less likely? I would think it makes it most likely that it's perfectly feasible for XMRV to regularly pass back and forth between mice and humans, but I guess it can also be argued that the labs that find XMRV have these variants of mice as a source of contamination (and running all over the CFS and PC samples but not the control samples for some reason...yeah, right...but they will say it...).

Next questions: where do the wild mice with these permissive receptor alleles tend to live? do these findings suggest that laboratory mice have aided the spread of XMRV? and can (P)XMRV infect (some species of) cats as well as mice, humans and monkeys?...

As far as I understand, XMRV has not been found in any mice so far...
This research is only demonstrating that some mice have cells that are susceptible to XMRV infection, in a laboratory setting.

For the sake of clarity, this research is showing that some mice have a gene which, in a laboratory setting, makes their cells susceptible to XMRV infection... The mice tested didn't have XMRV itself.