new Virology podcast on XMRV

[fresh_eyes]

Gosh, really, Esther12? Ever since XMRV came on the scene, nothing is more fascinating to me. (Before that, yech - I mostly just tried not to think about it!)

 

[Esther12]

Gosh, really, Esther12? Ever since XMRV came on the scene, nothing is more fascinating to me. (Before that, yech - I mostly just tried not to think about it!)

I'm the same, but I think my XMRV obsession is calming down now. It's balanced out with a cold, deathly fear that it won't lead to anything and we'll be sucked back to the medieval quackery of the last thirty years. I really wish we knew where this is going.

 

[fresh_eyes]

I went there, to the fear place, but that tide is turning for me now. The formation of the big HHS Interagency Task Force was very encouraging to me. Even - did you see this? - the person who started the "inconclusive results" thread finally got her results - positive. Which makes it 3 positive for both, 1 positive for culture only, 1 negative for both. I swear this thing is going to pan out. (I hope!!!)

 

[Martlet]

I too think it will pan out. I don't know for how many of us - there are still those XMRV negatives in sick people - but I think we are headed in the right direction. I wish I could afford the test, but I simply can't right now, otherwise I would be submitting my blood and taking my chances, because each one of us who can do it is advancing understanding of this disease for all of us - positives and negatives.

 

[Esther12]

Even if it just works out for 10% of the people with CFS, it would be enough to encourage some real research for everyone else. (Ideally I'd have something far easier to treat than a retro-virus!)

There doesn't seem to have been any movement on blood banks/donation/etc, and that worries me that things are not panning out. At the CFSAC (?) conference, they said there would be an announcement arround mid-Novemeber. I've not noticed anything like that, and you'd have thought there would be if XMRV was holding up. We'll see.

 

[fresh_eyes]

Even if it just works out for 10% of the people with CFS, it would be enough to encourage some real research for everyone else.

Exactly.

Did you see about the HHS task force I mentioned? It's about blood safety:

http://www.facebook.com/notes/the-c...ating-xmrv-scientific-activities/224210115538

And Wanda Jones tells us that 50 people are on the task force conference calls - surely not talking about how XMRV is turning out to be nothing, right?

 

[parvofighter]

Question

@George, Thanks for your great posts - I learn something every time I read them. Your comments got my creative juices going. Can you help me out here on the Dr Reeves question? I think there might be another angle to it:

I was surprised that he (Racaniello) got several of the details of the XMRV virus wrong in this podcast....The other was giving credence to the mouse feces way of transmitting the virus... But scientifically he must know that's not possible for several reasons.

First mouse feces taints nearly every processed food and is found on most unprocessed ground grown food plus, mice are ubiquitous to every home. This would mean that the WPI study would be completely invalidated as Dr. Reeves said because the virus would be everywhere.

I think Reeves' comment on the "virus being everywhere", invalidating WPI's work is a red herring
a) If everyone (normal controls + us) had XMRV (ubiquitous in that sense), would that invalidate WPI? Would it still be possible for only certain folks to get ME? Reeves would be wrong on that invalidating WPI. For example EBV is almost ubiquitous, and evidence of infection lies dormant in most of us. But it is well known that certain people (i.e. PWC's) can harbor persistent infections. The German cardiologists looking at viral cardiomyopathy know that too. It's not enough to find the virus on PCR. You also have to prove that it's active/reactivated (eg. immunohistochemistry). So just finding the virus in someone doesn't tell us a lot, and I suspect that that's what Reeves inadvertently meant. Thankfully one can now separate the two, and Reeves should know better.

b) If the virus being so omnipresent in ME/CFS patients is just an indication of sloppy lab practices.After all, tons of labs use mice in their research - the question was raised whether XMRV is just a contaminant. That could be another reason why almost all WPI samples had evidence of XMRV. From what I understand, that possibility has been ruled out because the genetic makeup of the virus in lab mice is significantly different from XMRV. And I think this is where Reeves was rather pathetically trying to steer us.

From what the researchers were implying, mice ARE everywhere our food supply is. No surprise really - it's just gross. One would think that these mice-to-human XMRV vectors could be happening all the time. Maybe they are. Or maybe a subtle genetic variation in one single mouse, litter of mice, or mouse virus, allowed the virus to jump species. Or maybe it's a simple and commonly occurring mouse virus mutation happening all the time from many mice, and because XMRV is replicating so infrequently, geographically disparate vectors still show up as comparable XMRV genome. I'm fuzzy on that - not sure if it's mouse evolution or mouse virus evolution that allows the virus to jump species...

My instinct is that Vince Rac is right that XMRV could have a vector from mouse poop to food to people (And I don't think that invalidates WPI at all). It does raise the question though of whether there is just one such vector, or whether this is still happening. And that gives me even more heebeejeebies about those occasional mice in our garage!

Third the virus is the same genetically in a twenty five year old sample as well as recently acquired samples. Differences of less than 25 nucleotides out of 8100 would indicate that this came from a single source.

First of all, where did u get this great info! Now the question: might these limited differences across samples just reflect how slowly this virus replicates? Maybe in 50, 100 years we might start seeing two significantly different XMRV strains that over time have differentiated. Kind of like continents moving apart, and identical species evolving into very different entities on their respective continents. I dunno, I think Vince was onto something, and I'd really like to hear your perspectives on the above!

Re: "catching XMRV". I've been trying to get my head around that, particularly as it relates to the outbreaks. I dug up Byron Hyde's Goteburg quote ( http://meagenda.wordpress.com/2009/...rv-retrovirus-in-goteborg-conference-address/ ):

"I should add that incubation period of XMRV is up to 21 days which makes it impossible to cause an epidemic illness.​

First of all, how could Hyde possibly know that? BUT let's imagine that his comment on XMRV's incubation period is in the right ballpark, and you can't get an epidemic with XMRV (as opposed to, say H1N1, which has an incubation period of 3-4 days) .

My theory is that you might "catch XMRV" a few ways:
1) You're born with it - i.e. your dad or mom had it, and this was passed down in the genome
2) You acquire it in the birth canal - exposure to bodily fluids transmission
3) You get it directly from a mouse-human vector by getting bitten by a mouse, or eating mouse poop (inadvertently, I might add)
4) You get it through unprotected sex or blood transfusion

Now as for how to "catch XAND", I think that's another matter. (And pure speculation on my part)
1a) You have asymptomatic XMRV, then get hit by another virus, and it activates the XMRV and/or the other virus somehow. Now you have XAND.
1b) You have asymptomatic XMRV, and another virus. Then you get massive stress, cortisol levels activate the viruses. Now you have XAND.
2) You and 4% of your town have XMRV. There's an outbreak of EBV (or other viruses). Up to 4% of your town converts thru the EBV to active XMRV. Now you have a XAND "outbreak".
3) You have another endogenous virus in your genome. You "catch" XMRV. XMRV and the endogenous virus activate each other. Now you have XAND.
And finally, likelihood of #1-3 happening goes up with environmental stressors, cortisol levels, exposure to toxins, etc.

What about remissions?
The fact that I and many others have had temporary remissions also speaks to some ability to either turn off XMRV or the opportunistic virus(es). THAT's what hugely interests me. And that is also what has me very interested in what the autism community is doing with diet/nutrition. Does XMRV in fact jump-start Autism? And is Jennie McCarthy maybe onto something? Very interesting stuff. Tho I admit I have had to willingly suspend disbelief - much like one does when watching a classic Bond movie. But if our own physicians had suspended their disbelief ages ago, imagine where we might be now.

Sorry about the long and drawn out response. But blame it on George. He started it!

 

[fresh_eyes]

Dang, you smart, smart people! Great discussion! I'll give it another read in the morning & comment.

 

[George]

Gezzz Parvofighter

I don't know if my brains in good enough shape to take all of that on. What are the questions specifically???

 

[Marylib]

Weenie retrovirus

Oh George, you got me laughing on that one!

The Weenie Retrovirus indeed


Actually that is pretty good to know! Better than one with a tough shell.

I am with Fresh Eyes -- you smart guys keep it up. It is fun to read. Even though I don't remember a thing!

 

[parvofighter]

Sorry George! 2nd time up to bat.

George & fellow forumers - sorry bout that brain dump. OMG it's my absolute worst weakness! OK, let me try to do the hardest thing in the world for me: summarize!

1) On reflection, isnt it possible that mouse feces contamination of human food IS a very logical mode of transmission? I dont see how this vector invalidates WPI. If so, how does it invalidate WPIs research?

2) If XMRV has differences of less than 25 out of 8100 nucleotides (across 25 years of samples, and across various geographic locations), couldnt this also be the result of just very slow replication?

3) Isnt it possible that one might indeed be able to catch XMRV and "CFS" as Racaniello stated? And same for XAND? Don't the EBV outbreaks that resulted in chronic EBV and ME possibly fit that definition? (I'd bet the incidence of CFS resulting from those outbreaks was < 4%. I.e. much of the previously unexposed population might have had acute EBV, but those who already had XMRV in their genome "caught CFS".)

4) And finally remissions. Might XMRV go into remission? But how could it if it's part of the genome and activated? Basically I'm trying to figure out how that could happen. Maybe Dr Luckett can help us out!

 

[George]

@George & fellow forumers - sorry bout that brain dump. OMG it's my absolute worst weakness! OK, let me try to do the hardest thing in the world for me: summarize!

1) On reflection, isnt it possible that mouse feces contamination of human food IS a very logical mode of transmission? I dont see how this vector invalidates WPI. If so, how does it invalidate WPIs research?

No it's not possible. The protein coat of the viral envelope will determine what the possible transmission modes are. Hard coats will allow for viruses to live outside the body longer like in feces, The thinner and softer the coating the less likely the virus will survive outside of blood or body fluids. Our lovely little XMRV has a very thin soft coating.

Part 2 the vector of mouse feces contamination would mean a much larger population in a much shorter time. For example, HIV was introduced into the human population from a small group of people (around a dozen) and took about 60 years to reach a pandemic level (around 10 million world wide). HIV and XMRV are much the same with HIV being hardier and more sneaky of the two. Now if you have a vector like mouse feces contamination that is ubiquitous then you have a large group of infected people in a short time. For instance H1N1 which became pandemic and infected 15 million in less than 7 months.

Our Illness goes back to at least 1934 and our numbers are around 17 million. That argues for a transmission type like HIV rather than H1N1.

2) If XMRV has differences of less than 25 out of 8100 nucleotides (across 25 years of samples, and across various geographic locations), couldnt this also be the result of just very slow replication?

Yes, it could and it is. That is the unique thing about XMRV. This retro virus is unlike HIV in the fact that it replicates with very few genetic variances. Which means that like the HPV (the virus that causes cervical cancer) they can whip up a vaccine for this in next to no time. However, if you have it then you will likely be stuck with it for however long the drug companies make money off of you. (grins)

But it still argues for a single source. (grins) Any virus that is transmitted from various animals in various geographical areas over various time periods would see differences in different sections of the genome. For instances mice with MLV in London are genetically distinct from the MLV found in mice in Florida with in the areas of the 5th and 7th gene sequence sections. These virus' are almost perfect with variations in only the 7th. That argues for a single source.

I'm going to take a nap now (big drooly grins) and come back to 3 and 4 in a bit if that's o.k.?

Thanks for asking the questions it makes me have to turn my brain on.

 

[_Kim_]

piggyback?

What about the idea that XMRV can piggyback onto other viruses (EBV)? Has this been ruled out as a possibility?

And my lack of knowledge of virology has me imagining our thinly enveloped retrovirus hanging onto the scruff of a bigger virus going wheee and hitching a ride inside a host.

 

[George]

I'm baccccccccccccckkkk (grins)

O.k. lets take on the next two questions then I'll take a break and come back and answer Kim.

3) Isnt it possible that one might indeed be able to catch XMRV and "CFS" as Racaniello stated? And same for XAND? Don't the EBV outbreaks that resulted in chronic EBV and ME possibly fit that definition? (I'd bet the incidence of CFS resulting from those outbreaks was < 4%. I.e. much of the previously unexposed population might have had acute EBV, but those who already had XMRV in their genome "caught CFS".)

It takes two set of factors that we know of or actually fit the theory and previous science, the first is a genetic predisposition and the second is a trigger virus. So you have XMRV, either you are a second (or third or fourth) generation baby or you really messed up sleeping with that good looking stranger one night, but either way you have the XMRV virus, from the little bit of science available looks like it might just go hang out on some globs of cortisol and drift happily around in your body without replicating (but that's not proven at this time) anyway you "catch" a virus like the flu and the XMRV wakes up and does the happy dance because you are providing a series of homes for it to move into and raise lots of baby's. T cells, B cells but most especially NK cells. So you are not "catching" XMRV you are activating it.

I'm guessing for the general population this may not make a lot of difference. Kind of a "don't yack at me about the science, just fix it!" so maybe I'm just being picky. If so disregard all of the above (grins)

The science gets really murky here, there are a couple of ways this could pan out from what I've read so far. One is that the change in the immune systems sets up a permanent activation of the immune response that leads to other imbalances, or possibly reactivation of latent endogenous retroviri that have been part of the human genome for thousands of years. Nobody really knows at this point exactly how it all works.

4) And finally remissions. Might XMRV go into remission? But how could it if it's part of the genome and activated? Basically I'm trying to figure out how that could happen. Maybe Dr. Luckett can help us out!

Probably, which is why in 67% of the patients the virus was found in active sera but in the 33% they were only able to find antibodies for the virus. Even in HIV there are remissions of active virus. Remissions give our body a time to heal until we pick up the next virus that activates the T1 response and starts the process all over again.

I hope that answered some of the questions. Or at least made what I was nattering on about earlier clearer??? Let me know, it's been fun.

 

[parvofighter]

By George, you've done it!

George, THANK YOU for so graciously responding to my questions! I didn't check in since last night, and then WHUMPH, two detailed and very helpful responses. Really appreciate you taking the time.

I feel kinda like the remora, hanging onto the underside of the shark's jaws, catching tidbits of yummy food as they float by!

Now it's my turn to go and digest what I've read... Thanks again!

 

[George]

Up next Ms. Kim

What about the idea that XMRV can piggyback onto other viruses (EBV)? Has this been ruled out as a possibility?

And my lack of knowledge of virology has me imagining our thinly enveloped retrovirus hanging onto the scruff of a bigger virus going wheee and hitching a ride inside a host.

(snort, snort) me too! Only I picture XMRV snuggled up to little globs of cortisol with it's little XMRV thumb in its mouth just waiting to grow up and be a big virus.

On the "piggyback" thing there are viruses that piggyback but usually to something way bigger than they are like fungus or bacteria. And in all my reading they are tough shelled viruses not thin enveloped ones. (shrug) I don't know enough and haven't been able to find out much on the web about this kind of thing. I know that only the one statement was made at CFSAC and that was pretty much the end of it as far as I tell. It doesn't look like Dr. Mikovitz has picked it up but you may want to ask Levi on that one. ???

That was a non answer kinda answer but it's all I know on the subject. Hope it helps.

 

[George]

arr, arr, arr, snort!

George, THANK YOU for so graciously responding to my questions! I didn't check in since last night, and then WHUMPH, two detailed and very helpful responses. Really appreciate you taking the time.

I feel kinda like the remora, hanging onto the underside of the shark's jaws, catching tidbits of yummy food as they float by!

Now it's my turn to go and digest what I've read... Thanks again!

That was cool word play, dude. (four paws in the air, waggin tail and laughing)

 

[_Kim_]

For those who don't want to cue up to the 30 minute mark...

luminescentfeeling has posted this podcast in two parts on youtube.

Futures in Biotech 50: Virology Blog (Part 1 of 2)

Futures in Biotech 50: Virology Blog (Part 2 of 2)

 

[_Kim_]

(snort, snort) me too! Only I picture XMRV snuggled up to little globs of cortisol with it's little XMRV thumb in its mouth just waiting to grow up and be a big virus.

What a visual!! You sure can paint with words George.

On the "piggyback" thing there are viruses that piggyback but usually to something way bigger than they are like fungus or bacteria. And in all my reading they are tough shelled viruses not thin enveloped ones.

How similar is the XMRV envelope to the HIV envelope? If they are alike, then from this article, we could extrapolate that once XMRV is in the host, that the co-infections (EBV, etc) could provide a piggy-back ride to organs that XMRV couldn't get to on its own.

Coinfections of human immunodeficiency virus (HIV), EBV, and HTLV or sperm proteins act synergistically to enhance infectivity and replication and expand cellular tropism. While some aspects of these synergisms are understood, others are not. We have found that membrane or surface proteins of CMV, HTLV, EBV and sperm proteins share large regions of similarity with the CD4 protein of T-helper lymphocytes. Since HIV uses CD4 as a receptor, it may bind to CD4 homologues on CMV, HTLV, EBV or sperm proteins. HIV could then piggyback with these viruses into cells with which it normally has no tropism.

 

[cfs since 1998]

On the "piggyback" thing there are viruses that piggyback but usually to something way bigger than they are like fungus or bacteria. And in all my reading they are tough shelled viruses not thin enveloped ones. (shrug)

Well, herpes viruses are the largest human viruses. Don't know if that means anything.