FDA and NIH confirm WPI XMRV findings (report of leaked presentation)

[Martlet]

Great that's my weekend ruined, spitting on babies &tongue kissing the elderly are my two favourite things to do!!! :tear:

Thanks for that Sickofcfs we need to keep laughing!

Jan xx

I was thinking more or less the same thing.:tear:

 

[judderwocky]

Okay folks, this is exactly why I don't think FeLV is the best model for comparison to XMRV. FeLV is strongly contagious through saliva and a group of cats (say in a shelter) can spread it among themselves fairly rapidly. We have NO evidence XMRV is transmitted this way and the pattern of illness suggests it is not highly contagious through saliva. If it were, we'd have a much larger infected group and much bigger outbreaks. All I had to do was mention FeLV is transmitted through saliva and WE, of all people, are starting to go off the rails.

We don't know, yet, how XMRV is transmitted, but it does not appear to be highly contagious. HIV is not highly contagious except through certain very specific routes. Blood to blood is very bad. Sexual transmission is somewhere about 1 in 10 exposures to an infected person. We could be contagious in the same way, although I'd expect to see more long-term sexual partners who both have ME/CFS. We'll know more when more people are tested for XMRV, though.

Also, I believe the incubation period, as in HIV, is fairly long. That means if you know you got something from a specific kiss, it isn't a retrovirus. You don't get sick within a few hours after exposure to a retrovirus. Even mono (in it's various forms -- EBV, HHV6, etc) has a 4-7 week incubation period, meaning you won't get sick until a month or two after exposure.

Some of the docs are talking about a double-whammy -- maybe you need XMRV plus something else to get ME/CFS. For example, herpesviruses (HSV, VZV, EBV, CMV, HHV6, etc) are known to reactivate each other an may have a similar effect on XMRV.

Or it may be as simple (hah!) as a genetic predisposition. Something in our immune systems doesn't deal as effectively with XMRV as other people's do, so they extinguish it immediately and we don't. If that's the case, we may be highly contagious, but it only matters if you're one of the 5% of the population who can't extinguish it.

As difficult as it is, we need to wait for the research. In the meantime, don't give blood, use safe sex, and maybe avoid spitting on or tongue-kissing babies, the elderly and others with weak immune systems.

beyond even that... resistance to retroviral phenotypes is largely a matter of genetics.... HIV and SIV are almost completely identical... yet HIV has a weakness to simian TRIM5Alpha, and SIV has a weakness to human Trim5alpha ... a key retoviral defense in mammals... the two forms of trim5alpha however were once distantly related... the evolution of these two different forms of the same defense molecule owes its current form to yet another endogenous retrovirus... PtERV1 (paleolithic endogenous retrovirus 1)... it turns out , our trim5alpha gave us complete resistance to this retroviruses, and the old world monkeys got screwed with PtERV1... on the flip side... they got resistance to HIV , no resistance to SIV, and we have no resistance to HIV... today they still have copies of PtERV1 in their dna ... about 130 copies on average... but the infection is not active... we however have no copies of PtERV1 in our dna...

its theorized that these mutations could have lead to distinct breeding populations... that essentially it was retroviral immunity vs. retroviral phenotypes that actually drove a portion of primate evolution.....

anyway... XMRV is not restricted by trim5alpha... which i keep saying is weird... because XMRV is something like 99% similar to MLV's which are restricted by trim5alpha.....


so as far as who is susceptible and who isn't... we have no idea... it could be something as simple as a homozygous recessive trait that gives someone a recessive defense mechansim.... maybe that would explain why some carry the virus and do not get sick... they are partially susceptible but with at least one workign copy of a correct defense molecule their body can still manage....

 

[bullybeef]

I asked this earlier but may have been missed. How is MLV transmitted? Does no one know?

 

[kurt]

I asked this earlier but may have been missed. How is MLV transmitted? Does no one know?

The general view in the studies I have read is that it usually requires blood transfer. That pretty much rules out outbreaks (unless the virus is already present of course, and some event acts as trigger). There is one study that proves MLV can be an STD in an animal model. That was a study of 'Murine AIDS' (MAIDS), which is an MLV retrovirus infection. see: http://jvi.asm.org/cgi/reprint/72/3/2541.pdf

 

[judderwocky]

The general view in the studies I have read is that it requires blood transfer or vertical. That pretty much rules out outbreaks.

i think its too soon to rule anything out. for one tropisms for viruses change from one species to the next, so because its transmitted a certain way in a particular animal, we can't be certain that will carry for over for others... it will obviously be similar, but there are differences, sometimes developed specifically for protection against viruses, between species that allow certain cells or classes of cells immunity... for instance primates use vitamin d in their epithelial cells to generate amp sequences like cathelicedin...mice don't have this advantage, its a primate only thing we had to develop because our respiratory tract is upright... it goes farther though... signalling proteins that viruses use to enter cells are not always present in other species, or sometimes have evovled to the point where they are just too different. additionally xmrv has already been shown to be dissimilar to mlv in restriction by trim5alpha... until we know what defense mechanisms and what cells xmrv can target... we really have no idea of knowing what tissues and what types of behavior can spread it.

a weird point of interest... something i noticed ... if you look at a text book of which animals carry immunity to mlv... a lot of them are things like... snakes... cats, humans,.... animals that are supposedly more susceptible are those that have had less contact... like non predatory bird species, horses...

it makes sense that animals that prey on mice or come into contact wiht them woudl have to develop immunities to viruses that they carry..... who knows

a lot of ancient cultures have reliefs and paintings of rats as plague bringers and harbringers of famine and pestilence... ancient Olmec scenes have been shown... the Mautan in Southeast Asia (i think spelled that wrong) is known as the cyclical rat plague that descends every 50 years with the ripening of bamboo flowers.... every culture hates these things....

 

[taniaaust1]

Great that's my weekend ruined, spitting on babies &tongue kissing the elderly are my two favourite things to do!!! :tear:

Thanks for that Sickofcfs we need to keep laughing!

Jan xx

I like to tongue kiss the elderly .. im in my 30s and my partner is in his late 60s , possibly 70s (lol my memory is bad). I chose to get an elderly boyfriend as i wanted to be able to keep up with my lover. Darn it thou, i still cant keep up with him. I think i'll go for someone over 100 next.

 

[Eric Johnson from I&I]

> it could be something as simple as a homozygous recessive trait that gives someone a recessive defense mechansim

Maybe. If there is an allele of large effect it should have shown up in segregation studies, pedigree studies, whatev (I forget what they are called properly), even though the penetrance is probably well below 100%. *If* any such studies have been done, that is. I'm not sure any have been. (There certainly haven't been any GWAS in CFS and I'm not sure any other major diseases have been left unstudied in that regard.)

 

[sproggle]

This been posted yet?

http://www.cdc.gov/eid/content/16/6/pdfs/10-0066.pdf

"Our findings indicate that XMRV or virus-infected cells might be carried in and transmitted by the respiratory tract. Attempts to isolate infectious virus from XMRV sequence–positive respiratory samples failed, possibly because of inadequate storage of samples before virus culturing attempts or relatively low copy numbers of the virus within the samples. Thus, whether the respiratory tract serves as a putative transmission route for XMRV cannot be determined at this time. The observed increase in prevalence among immunosuppressed patients with RTI suggests that XMRV might be reactivated in absence of an efficient antiviral defense. Together with earlier observations on increased XMRV replication in RNase L–deficient cells (1,12), this finding implies that the immune system plays a role in controlling XMRV replication. It remains unknown whether immunosuppression predisposes a patient to secrete infectious XMRV from the respiratory tract or whether presence of virus might be meaningless for epidemiology in a way similar to HIV-1 (15). Future studies should address whether the respiratory tract might serve as a source of XMRV infection or whether immunosuppression might cause an increased risk for primary infection."

 

[bullybeef]

With the conjecture that XMRV is maybe spread via saliva (and I do remember Cheney suggesting this maybe the case last October), and the obvious counter statement that "everyone would have it", could it be that it is only infectious in saliva at certain periods (life cycle)? Therefore this could explain outbreaks in close knit communities.

 

[judderwocky]

I think thats the kind of thing they were looking into Rnase L for .... perhaps not even an outright bad mutation, but maybe a weak gene or allele that breaks or something sporadically...
Rnase L defeciencies were the original link that drew the pc and CFS patients groups together....

who knows... with six different phenotypes already demonstrated we could have a very diverse set of immunities, and possibly even transmission methods....

we just don't know of any other gammaretroviruses to infect humans..... i guess thats a good thing... keep telling myself its soo great that were trailblazers.... isn't?

---

R462Q RNASEL is the homozygous characteristic that originally got them looking at XMRV in CFS patients.. when they saw it was correlated to PC and XMRV, they thought hey, CFS patients have faulty RNase L why not see if they have xmrv

 

[Eric Johnson from I&I]

anyway... XMRV is not restricted by trim5alpha... which i keep saying is weird... because XMRV is something like 99% similar to MLV's which are restricted by trim5alpha.....

I could be wrong but I'm pretty sure it's much less than 99% identity. Anyway, probably only one amino acid change is need to abolish the liason with this trim5 varmint, as long as it's the right aa change.

I quite agree with your broader point. The ability to make inferences by analogy here is very limited; devil's in the details.

 

[omerbasket]

I think that I've recently read that XMRV is 96% similar to MLV's.

 

[judderwocky]

woops... you're right... 95%....that extra five percent seems like it means it would be hanging out in the population for a while.... im trying to process the implications...

 

[usedtobeperkytina]

Seems to me, that since it is in the blood, disappears and then goes into cells, then moves around to different types of tissue (see the macaques study), I would think there is period it can be passed in blood, then not. Possibly, then, a time of replication, immune system down, it goes into the blood again. (has to travel to other tissue somehow.)

It seems the disappearance in the blood may have to do with immune system response to it. But, there may come a pivotal point, as in HIV, where the damage done to immune system is too much for antibodies to get back under control. But since this virus has triggers (progesterone, cortisol, etc.) then it might go dormant, or at least not be replicating much. Immune system has it under control. But another trigger happens, and immune system loses ground again, symptoms come back, it's out in the blood again. Mikovits spoke about the sudden cytokine response, like you're walking in the grocery store, and a flood of cytokines are released.

So the flood helps in getting the virus under control again. It is at low level. Isn't floating in the blood. But then, we feel better, we do some cortisol stuff, or our progesterone goes up with monthly cycle, and there we go again. Another round.

So maybe infectivity, saliva and blood, comes and goes. All matches to our good days / bad days scenario and the chronic nature, as opposed to HIV, that just gets in, keeps replicating until immune system keeps up, two years later, if no treatment, person is dead from co-infection or cancer.

Which brings up the other issue. I agree that FeLV is likely more transmissible than XMRV. But relating to HIV would bring fear of imminent death if no treatment. And HIV has connotation of immoral activity. So I don't like that comparison.

Any other ideas. I thought FeLV was most like XMRV, in that many cats have it but don't get sick. It causes immune system and cancer problems. Of course, if a cat has the immune system problem with FeLV, very likely, that cat will die. But some have a mild form.

Can we say XMRV has some features similar to HIV and some similar to FeLV?

Got to come up with something.

Tina

 

[judderwocky]

I could be wrong but I'm pretty sure it's much less than 99% identity. Anyway, probably only one amino acid change is need to abolish the liason with this trim5 varmint, as long as it's the right aa change.

I quite agree with your broader point. The ability to make inferences by analogy here is very limited; devil's in the details.

also... i do believe a number of the trim5alpha mutations are pretty close like that...

i can't wait for them to do some really good phylogenetic analysis on this ... and maybe then we will know, how long its been here, how long we've had it, ... right now nobody is even completely certain we aren't getting it directly from mice... or mosquitos... who knows... is there any reason anybody could think of that this isnt' actually Squirrel Leukemia Virus... or any other mouse like creature...

i really have no idea if squirrels are even that closely related... but there are a lot mouslike varmits out there... maybe MLV just happens to be teh closest relative of something that is incidentally infecting people through a vector... say a mosquito? that would explain why only some familiy members get it.... or why it breaks out in a single institution... fllees maybe in conjunction with squirrels.... or bats.... ?

say MLV disassociated from XMRV into say, squirrels or some other rodent ... maybe a thousand years ago... long enough to pick up additional mutations...

the only problem is, that our trim5alpha usually gives us resistance to retroviruses that are further away from us... trim5alpha does a good job with things that aren't HIV... so it would seem if XMRV can get around it, it would be something less likely to just be jumping across species through a vector so rapidly --- *just ignore that logic hole


whatever... im just widely speculating... there are so many holes in all of this its moot. lul

 

[Eric Johnson from I&I]

I'm getting pretty crabby now... GIMME THAT PAPER!!!!! I think if I knew what journal it was, I'd drive there and slink into their editorial office.

 

[Eric Johnson from I&I]

Then I'd photograph each page of the paper with a 007 bowtie-camera.

 

[Eric Johnson from I&I]

And though I'm not crabby enough to kill, I might try to beat someone up a little on the way out, in the unlikely event that I should come across a male skinnier than myself.

 

[judderwocky]

rofl... retroviruses are for ever

 

[Eric Johnson from I&I]

Just give publish the paper for Pete's sake and there won't be any trouble Mister.