XMRV: exogenous and/or endogenous?

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George

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It fits perfectly

Wow this simple question is proving to be a tough one to pin down!

What George said makes sense, but how does it square with the quote Advocate picked out from the NCI Q&A?

""When retroviruses infect germ cells (sperm or egg), endogenous viruses, can develop. The integrated viral DNA, or provirus, is passed from parent to offspring. There is no evidence suggesting that XMRV can do this in humans."

I read that as saying that if XMRV were to infect a germ cell, that could put it in the DNA of offspring and result in an endogenous virus. The only way I can square that with George's post is if, when they say "can develop" they mean "can develop 100 generations later", but that seems a bit of a stretch.
Let say you have billions of XMRV virons or virus partials swimming around in your blood busily infecting the cells it likes best. What are the chances that a virus will actually infiltrate a sperm or an egg cell? Fairly small actually since both the egg and sperm are coated with a specific protein that protect them and they are both in very protected areas of the body.

Now what are the odds that the infected sperm or egg would go on to become fertile and produce an offspring? Considering how many eggs pass through without fertilization and that only one sperm out of millions will fertilize any one egg the numbers become inestimably tiny. That's what is necessary for virus or retrovirus to become Endogenous. It happens, but it takes a really long time, minimum a hundred generations. and . . .

The retrovirus itself must change and be able to pass barriers around ova and sperm production sacs. Plus the virus must be able to pass through the barrier of the sperm or egg itself and that's a whole complex protein structure in itself.

Right now however the versions of XMRV that are being passed around are stimulated by cortisol and due to the envelope around the virus are able to slip in undetected in T, B and NK cells for sure and probably some others that we don't know about yet. But the changes necessary for it to infect the "germ line" (egg and sperm) are not there at this time. thus;

""When retroviruses infect germ cells (sperm or egg), endogenous viruses, can develop. The integrated viral DNA, or provirus, is passed from parent to offspring. There is no evidence suggesting that XMRV can do this in humans."
There's no evidence it can become Endogenous at this time.

But we are passing live virons down via blood, and milk to our children. And we are passing it via sexual transmission to each other.

These scientist are talking to other scientist and figure that all of the middle parts are understood so it's left out of the writings. The other confusing thing is that this is a new retrovirus. Scientist deal in facts and won't make a statement that they can't back up. They get major slapped down if they do. So they leave out any thing that they don't have iron clad, double blind study to back up. Heck there's doctors still disputing the mechanisms for HIV.

Have you ever been asked the math question ;

If you start out with one penny and you double the number of pennies each day how many day's will it take you to reach a million dollars?​

Now think about it like this;

If you have one person with XMRV and that person passes it on to one other person.
Each of those person pass it on to one other person.
It's in effect like doubling the pennies only it takes much longer.​

So you can create a pandemic long before the retrovirus has a chance to fade into the human genome.

I hope that was clear. If not say what's not and I'll try to clear it up some more.
 

Mark

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Brilliant explanation George, thanks a lot for that, I'm happy now! Sounds like we can rule out any considerations of endogenous XMRV.

Only question I'm left with (a mere technicality) is this one:

Wouldn't it be "endogenous" in some people during that time - or is it only endogenous when the entire human race has it in their genome?
I think you've pretty much answered that really, that it's only endogenous when it's no longer harmful, and I guess by the time that's had chance to happen it would be universal in the human race?
 

fresh_eyes

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Sounds like we can rule out any considerations of endogenous XMRV.
Whew! OK!

But still an open question is, does XMRV reactivate potentially harmful endogenous retroviruses (per the study cited in the article that begins the thread). Right, George?

Which would make XMRV exogenous but XAND maybe an exo/endo combo. The "genetic predisposition" aspect of it it all might be ERV-related. Right, George???

Thanks for the great discussion here guys.
 

Advocate

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Thanks for posting this fresh eyes.
I'm currently in an HERV K18 study Dr. Huber is doing.
Shelley
I see that she's in Boston, at Tufts--same as John Coffin-- and you are in the Southwest. In any case, this opens up a whole new world of interesting google alerts.
 

Advocate

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As a computer programmer, I instinctively thought of the 8% as effectively functioning as a kind of memory bank of old infections. On the one hand, the story is that retroviruses inflitrate the immune system and eventually survive as endogenous DNA code, and I then imagine that evolutionary pressure, and some other mechanism, eventually combine to 'switch off' any harmful endogenous code in the human genome. But on the other hand, it's interesting that the deactivated code remains in the genome: is it put to any use?

Of course one can easily imagine why the body might have no mechanism for getting rid of such bits of code in its DNA, but I would tend to suspect that in evolution, nothing is wasted, and this bank of information could feasibly be very useful to the immune system. As an idea of the type of thing: is it possible that the immune system consults this bank of ancient retroviruses when it encounters a new molecule for the first time and has to decide whether to create antibodies for it or not? Something along those lines.
Maybe you could ask Vincent Racaniello, PhD, about that. Or maybe he already says something about it on his website:

http://www.virology.ws/about/

Dr. Racaniello is a professor of microbiology at Columbia University Medical Center, and his website includes a free Virology 101 course, which I've started on, but I haven't gotten to endogenous retroviruses yet. I'm still in the looking-at-pictures stage.
 

Advocate

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The retrovirus itself must change and be able to pass barriers around ova and sperm production sacs.
Yes. That squares with all the little videos I've been watching of viruses (not retroviruses, specifically) hooking up with the outer cell wall, like a space ship landing on the moon, before it's schlurped into the inside of the cell. All of the parts have to fit just right before it can get in.

I LOVED your explanation.
 
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George

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Wow that's a lot of questions (grin)

Hi George. Thanks for your very lucid explanation about endo vs. exo. That fits with understanding as well, though I suspect there may be more yet undiscovered in that field. One question, though - how does your explanation fit with the quote from the top of the thread:

"This new retrovirus [XMRV] may be able, through infecting human cells, [to] induce a transcription of an endogenous virus," says Huber, who has been studying the presence of an ancient retrovirus (HERV-K18) dormant in most people but active in patients with CFS and multiple sclerosis. "We've already shown that Epstein-Barr virus can do exactly this."​

My understanding of this was that EBV has been shown to re-activate the endogenous "ancient retrovirus HERV K-18", and they wonder if that reactivated retrovirus then begins to "cause problems" again, at least in combination with the EBV (or maybe XMRV). Or no? I thought that was the point of that research.
First of all let me put my 'creds' up. My parents wanted me to be a doctor, so I did the pre-med thing. Lots of biology, zoology, and virology BUT In my third year my professor told my parents that I would not get accepted to med school because my Vita wasn't properly rounded out. I was so happy!
So I have a really good grounding in the sciences but some of this stuff is way over my head guys. I'll jump in if I think someone may be going down the wrong track because I don't want anyone to say something to a doctor and get slapped down for it or be dissapointed later on down the line.

but I'm like you guys I'm just waiting for the science. There's not enough of it yet to really 'do' anything with yet. (grin)

Having said all that on to the HERV-K18 question. I really don't know. I'm still reading up on it so I can't say one way or another if it fits or not. I think we'll just have to wait and see. Sorry Fresh eyes.
 

SeaShel

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I see that you answered my question in your post #14. Very interesting!
Hi Advocate -

To further clarify (if my fog is not clouding what you're asking), I get the study questionnaire in the mail ahead of time.

A phlebotomist comes to my home to do the draw.

Within a few hours, the research aide calls and I report my answers to the questions and that's it till next time.

They are very considerate of time and energy levels in the scheduling.

The only confusing thing is that I've been told different things about what all they are looking at in the blood work. Guess we'll just have to wait for the paper and see what all it reports.
 

fresh_eyes

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...on to the HERV-K18 question. I really don't know. I'm still reading up on it so I can't say one way or another if it fits or not. I think we'll just have to wait and see. Sorry Fresh eyes.
Well, med school's loss is our gain here, George - thanks SO much for sharing your knowledge. I think it's great to get to the limit of what's known so far, so we know what we need to know! Do let us know when you get the HERV K18 question solved!:D
 
G

George

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O.k. here goes

You guys are a kick. O.k. in regards to what Dr. Klimas statement about transmission. It's to bad that she didn't have time to clarify a lot of what she was talking about but she really tried. So, I'll try to fill in the blanks.

Remember that Dr. Klimas works with AIDs patience's so she knows a lot about how AID's is transmitted in the population and, how it is triggered once it infects a host/person. She's also cutting edge on virology in general so based on what she already knows she's formed a theory. It is however, just a theory and is only partially backed by science at this point. It's still early, early days yet.

The virus is passed with semen they know for a fact. This is a big distinction, it is passed side by side with semen, it is not able to breach the barrier of a sperm and therefore be passed IN the semen. That's the difference between the virus being endogenous and exogenous. Endogenous the virus would be inside the sperm cells. That's not the case with XMRV. It's unable to penetrate the sperm envelope. It is however passed in the fluid that moves the sperm.

O.K. So the male has intercourse with the female and passes both sperm and live virus onto the woman. The live virus doesn't stay in the vaginal and uterine track but instead is absorbed into the blood stream. Once XMRV is in the blood stream it hangs out in a dormant state until there is a triggering event.

When a pregnancy occurs in the woman the first thing to note is that the egg does not have the XMRV virus in it. Ova or eggs are seriously tough packages, there is very little that gets to them except the occasional lucky sperm. The XMRV virus is however, in the mothers circulatory system; therefore it does get shared in the placental fluid. When the virus enters the baby's developing circulatory system it will (hopefully) be in a dormant state and no problem for many years or decades to come.

This virus probably entered the population around 100 years ago or about 5 generations ago. There were probably at least a dozen people who originally contracted the XMRV virus from mice. Remember the XMRV virus is a mutated version of MLuV or Murine (meaning mouse) Leukemia (because it used to cause leukemia in mice) Virus (because for them it is Endogenous it doesn't cause any problems for mice.)

So let's say your great, great grandfather worked in a lab that had a breed of mice that had the mutated virus, let's say that great, great grandpa has 2 girlfriends before he meets and marries great, great grandma. Great, great grandpa has now infected 3 women. Great, great grandma not having birth control now has 7 or 8 living children. The other women that great, great grandpa slept with also have 7 or 8 living children. From just great, great grandpa there are now 3 women plus 20 or more children who have the live XMRV virus in just one generation. And remember great, great grandpa was only one of the dozen (or more) people who originally contracted the virus. So in one generation you now have around 200 to 250 people infected and that's a minimum.

Some people develop, what back then was know as neurosynthisa (spelling??) but I can hear the doctors now 'heck; it just the women being tiered 'cause of all them kids their popping out' (my words not science here). The next generation would have been between 1920 and 1930. So your great grandparents met up and one of them was infected and passed it on to the other, as well as all of the children. Assuming all of the other folks that were infected from the first generation do the same thing. Meet, marry and produce offspring then the second generation would have a minimum of 5,000 to 6,000 infected individuals. That's not even factoring in the fact that some of those individuals might have more that one sex partner.

Again some people developed symptoms and were probably written off due to the fact that any one doctor would not have seen enough cases to establish a epidemiology. Your Grandparents generation would have seen in the area of 100,000 to 150,000 persons infected (BTW I'm going by the extrapolated numbers for HIV infection) still not enough to arouse any notice from the medical community.

Now your parents generation had fewer children due to birth control however they had more sex partners. Those sex partners had children of their own as well as possible other partners so you are now looking at an infected population of minimum of 1 million people. Again some had triggers and some didn't but not enough to alert the medical community.

Next we come to our generation starting about 1950/1960. (if the numbers hold up, could be more or less) Figuring in blood transfusions, sexual habits, family sizes, there are now probably around 27 million XMRV carriers. Remember that this is speculation based on the study of the HIV pandemic times, and transmissions. There are no hard numbers on CFS/ME/CFIDS. Now if you take the 27 million number and times it by 3 sex partners (the average in this day and age) and then take that number and times by 2.25 children (the average world wide) then the next generation is looking at 182 million infected people in the next twenty years.

And of course XMRV doesn't always express itself as CFS/ME/CFIDS but as MS, autism and probably a few other things that we don't know about yet. The thing is if a retrovirus hadn't been discovered these kind of numbers would never have been considered. Nor would anyone be looking at numbers of Neuroimmune illness's instead of each separate group.

Again all this is theory with very little scientific study to back it up at this point. But because of HIV they have avenues lined out to explore.

Hope that wasn't to long or too boring. (grins)
 
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You guys are a kick. O.k. in regards to what Dr. Klimas statement about transmission. It's to bad that she didn't have time to clarify a lot of what she was talking about but she really tried. So, I'll try to fill in the blanks.

Remember that Dr. Klimas works with AIDs patience's so she knows a lot about how AID's is transmitted in the population and, how it is triggered once it infects a host/person. She's also cutting edge on virology in general so based on what she already knows she's formed a theory. It is however, just a theory and is only partially backed by science at this point. It's still early, early days yet.

The virus is passed with semen they know for a fact. This is a big distinction, it is passed side by side with semen, it is not able to breach the barrier of a sperm and therefore be passed IN the semen. That's the difference between the virus being endogenous and exogenous. Endogenous the virus would be inside the sperm cells. That's not the case with XMRV. It's unable to penetrate the sperm envelope. It is however passed in the fluid that moves the sperm.
.................

Hope that wasn't to long or too boring. (grins)
Hi tina - big grins back from me and my dog

You have an AMAZING ability to explain science in a way that lay people can understand. Hope you use this gift outside the forum! It's rare.

I still can't read much, despite on-going efforts, so I couldn't get much beyond the line I marked above.

My lay-person question is, if xmrv is passed with the fluid that moves the sperm, isn't that fluid generated in the prostate? Could this have something to do with the prostate cancer results?
 

Marylib

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George (and T.) Outta the park

Wow! That was dynamite. Why didn't I have science and math teachers like you...well done.
Applause applause!
 

gracenote

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endo and exo illustrated

Hope that wasn't to long or too boring. (grins)
I think I got it, by George. Great explanation. I would love to have read it along with some illustrations drawn by Priscilla Gilman. You two would make a great team in writing a guide called XMRV Made Easy, or Endo and Exo Illustrated, or something like that. Anyway, good job George. And for those of you who haven't already, you might like to check out this website.

http://www.heaveninmyfoot.com/2009/10/xmrv.html
 
G

George

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Bingo!

Hi tina - big grins back from me and my dog
That's so cool. My dog sends your dog a tail wag!

[/QUOTE]My lay-person question is, if xmrv is passed with the fluid that moves the sperm, isn't that fluid generated in the prostate? Could this have something to do with the prostate cancer results?[/QUOTE]

You got it in one. Yes, it was during the prostate cancer study that they found the virus was moving from the prostate via the semen. That's one piece of science they know for sure.

The other piece is that they know for sure it's blood born so it is transferred in any blood or blood serum fluid like breast milk and most likely the placenta that feeds the fetus (but no hard science on that yet).
 

Mark

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Won't hurt to say it again, George your explanations are sensational! They really are a breeze to read, you're pitching it perfectly. Just hope you're not making a rod for your own back here...

My next question is: given you've established that XMRV can be passed male to female (amazed we're only just now unearthing that confirmation of a crucial transmission question), what's the story going back the other way? (George draws another deep breath...). If that were impossible or unlikely for some reason, could that explain all the differential rates of CFS for men and women?

btw, reminder that the MS rates are especially interesting because for people over 50 they are 50/50 but after that they start to affect women more than men. (MS onsets in early adulthood dating start of this change to 1980s as well).
 
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anne

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I love these very clear posts. Thank you guys. All I can add to the discussion is that in our case, it was definitely passed she-to-he, so it happens.