I can't guarantee that this blog is 100% accurate because I'm not an expert in mouse virology! But I think it's all accurate, after having done some heavy-duty reading about it all. This is purely a discussion of my understanding of the subject, as a lay person.
Any comments or corrections are welcome.
Update: I made an error in this blog regarding the behaviour, and method of transmission, of X-MLV's in X-MLV resistant mice. Thanks to Dr Yes for pointing out that whole X-MLV's are formed in X-MLV resistant mice, whereas I had thought that only partial viruses, or viral particles, could form in this type of mouse. Please see Dr Yes's post in the discussion thread, below, for the correction and some further useful clarifications.
I have corrected the blog and added some clarifications, extra info, additional notes and my sources, and it is now accurate to my best knowledge, with some further clarification from Dr Yes in his post below.
Apologies for the incorrect information. I had warned that there may be inaccuracies, because I'm a lay person (ME patient) and not an expert in mouse virology, but apologies anyway.
The reason for my confusion is that I had thought endogenous viruses could not form whole, fully active, viruses in the host species, but it seems that this is not (always) the case. No human endogenous viruses form whole viruses.
XMRV is purely a human virus, as per as our current knowledge, and it has never been found in mice, so far.
The confusion about whether XMRV is a mouse virus or a human virus arises because XMRV is very similar to MLV's, which are mouse retroviruses.
The similarity to MLV's is where the name comes from:
X - Xenotropic
M - MLV
R - Related
V - Virus
So, XMRV is an MLV-related virus. This means that XMRV is related to MLV's but it is not an MLV itself because MLV's are mouse viruses, whereas XMRV is a human virus... A new human retrovirus.
Another reason for some of the confusion is the use of the 'X' or 'Xenotropic'.
The 'X' ('xenotropic') in 'XMRV' refers to the behaviour of MLV's and indicates that a virus can infect, and replicate in, the cells of a species (e.g. in this case, humans) other than the original host species (e.g. in this case, mice), but that it cannot infect the cells of the original host species (mice). Actually, since the naming of these xenotropic viruses, it has been discovered that the Xenotropic virus behaviour only applies to certain strains of mice, and that some mice have cells that are susceptible to infection by these viruses (more on this below.)
In the case of XMRV, the 'X' ('xenotropic') is referring to the name of the mouse viruses (X-type MLV's) that XMRV is similar to... The 'X' is not referring directly to the behaviour of the new human virus 'XMRV'.
So, in other words, the X-type MLV's, that XMRV is similar to, can infect other species other than the original mouse host, but they cannot infect the cells of the strains of mice that the 'Xenotropic' name applies to (other strains of mice do have cells that can be infected.)
So a question arises: "How can a mouse virus exist in these mice the first place if it cannot infect the cells of the mouse host?"
This is where it gets even more confusing!
'X' type MLV's (Xenotropic MLV's) are 'endogenous' retroviruses. An endogenous virus is not an independent virus, but exists as an integral part of the host species' DNA. Evolutionary process have meant that a retrovirus managed to insert it's own DNA into the mouse DNA (retroviruses replicate by inserting themselves into the host species' own DNA) and it has then entered the DNA of the germ-line cells (sperm and egg cells), and the virus DNA has been passed into the DNA of every cell of the next generation of mice... Over time, the endogenous virus becomes widespread throughout the whole of the species.
So, endogenous retroviruses are encoded in the DNA of the host species.
It is possible to check to see if XMRV or PMRV are lab contaminants from either mouse DNA, or endogenous mouse retroviruses, by checking the genome of XMRV or PMRV against the mouse genome. If the XMRV or PMRV genomes were found to be encoded in mouse DNA, then their discovery might have been due to mouse contaminants, but they aren't in the mouse genome, and there are also many other reasons why XMRV and PMRV have been shown not to be contaminants.
Mouse DNA includes the DNA of endogenous mouse viruses (MLV's) which is why alter checked the genome of his PMRV's against the mouse genome, to see if the PMRV's he detected could be due to contamination from mouse MLV's (endogenous mouse viruses) or mouse DNA. The PMRV's genetic code didn't show up in any of the mouse genomes tested.
The reason that these particular mice cannot be infected with their own endogenous X-type viruses is probably because they have evolved a resistance to infection (see additional notes for clarification). This resistance is achieved by a mutation in the DNA which encodes for the relevant cell wall receptor which the virus would attach to. This means that the MLV cannot attach to the cell wall and gain entry to the cell. However, the endogenous retrovirus DNA, as an integral part of the mouse DNA, can still encode for these viruses, and the mouse cells can create spurious viruses which get pumped into the blood stream. In the resistant strain of mice, the viruses are unable to attach to the mouse cell walls, because of the evolved resistance, and therefore cannot infect, or enter, new cells. It is possible for these viruses to jump species, however, where they can then become fully active and replicating viruses in the new host species. If the mice were to lose their genetic resistance to their own endogenous retroviruses (retroviruses encoded in their own DNA), then the mouse's own DNA would encode and form complete retroviruses which could then infect other cells of the mouse, because there would then be no genetic resistance inhibiting infection by the virus. This would probably be the case in the non-resistant strains.
The 'X' in 'XMRV' refers to a type of MLV virus (Xenotropic MLV) that was already known to science. However, it seems that the 'X' is now a loose term because, since the naming of X-MLV's, more research has been carried out which demonstrates that these viruses behave differently in different strains of mice. Some strains of mice have now been demonstrated as being susceptible to infection by X-type (xenotropic) MLV's because of a genetic difference that alters the relevant receptor of the mouse cell wall. So it seems that 'X' has become purely a name, or categorisation tool, rather than an indicator of function in the wider mouse population. Indeed XMRV also has P-type MLV genetic code in it anyway. 'P' indicates polytropic virus behaviour which means that the virus can infect the cells of the original host species as well as being able to jump to a new species.
We hardly know anything at all about XMRV yet and it's helpful to know as much as we can about it, including whether it is purely a human virus, or a cross-species mouse virus. Knowing for certain that the virus is not present in any mice also helps to prove that XMRV is not a lab contaminant originating from mice.
Some recent research has demonstrated that certain strains of mice are genetically susceptible to infection to XMRV in laboratory conditions, although no XMRV has ever been found in any mice 'in the wild'.
We can't be 100% certain that XMRV is not harboured by any mice because there are so many different varieties and populations of mice in the world, including wild and domestic and lab mice. This means that certain strains of mice are susceptible to different viruses, and diverse mice populations might be exposed to, and harbour, different pathogens.
XMRV has never been found in mice, but it is similar to mouse viruses, so it is possible that XMRV might be hiding in some small mouse population, somewhere. However, at the moment, it looks like XMRV is purely a human virus which probably originated in mice... If this is the case then a mouse virus would have crossed over to the human species at some point in our history, and then the virus would have mutated so that it easily passes from human to human, and easily replicates in humans. When it mutated, it became purely a human virus, as long as it is not passed back to the mouse population. If it is found in the mouse population then it will be a cross-species virus.
One other thing to mention (thanks to anciendaze for pointing this out) is that there could be an intermediate species, between mice and humans, where XMRV originates from. In other words, an MLV could have jumped to another animal species, from mice, where it then mutated into XMRV. And then XMRV could have jumped to humans from the intermediate species.
This is such a complex subject area.
The earliest study I can find on Xenotropic viruses is authored by Jay Levy, dated 1973: http://www.ncbi.nlm.nih.gov/pubmed/4356281?dopt=Abstract&holding=f1000,f1000m,isrctn
Referring to a Xenotropic virus, the paper says: "it grows only in cells foreign to the host."
This early definition of 'Xenotropic' led me to my earlier error that whole Xenotropic viruses could not grow in mouse cells. Levy's 1973 paper was early research, and the author doesn't seem to be certain that the Xenotropic viruses are endogenous in the strain of mice that he studied, but further research studies show that production and release of Xenotropic endogenous mouse viruses occur spontaneously from the resistant mouse cells.Earlier in my blog, I have said that the resistant mice owe their resistance to xenotropic viruses due to an evolutionary process. This would mean that sometime in the history of that strain of mouse, a evolutionary selective mutation occurred to the mouse DNA which encoded for the relevant receptor on the mouse's cell walls which made the cells insusceptible to the Xenotropic MLV's. This is said to be the most likely reason for the insusceptibility to infection, but it is also possible that the virus originally infected the mouse using a different receptor.One of the most simple, authoritative and accurate explanations of the meaning of 'xenotropic' is that xenotropic viruses "do not recognise a receptor on cells of their hosts."
http://books.google.co.uk/books?id=...ruses&pg=PA360#v=onepage&q=xenotropic&f=false (Page 360)
One other thing to add to the discussion is that one paper reports that the 1973 study by Jay Levy discovered that the endogenous xenotropic retrovirus he was studying could infect humans... So why did it taken another 33 years to discover XMRV and PMRV's?
http://books.google.co.uk/books?id=...ruses&pg=PA360#v=onepage&q=xenotropic&f=false (Specifically Page 360)
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XMRV - Human Virus or Mouse Virus? Technical Explanation.
Blog entry posted by Bob, Oct 22, 2010.