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Interesting XMRV research funded by NIH

Jemal

Senior Member
Messages
1,031
This project got 1.5 million dollars.

The gammaretrovirus xmrv has been isolated from patients with prostate cancer and more recently with chronic fatigue syndrome (CFS) and in children diagnosed with neuroimmune disorders.

The NIH has sponsored CFS research for many years and is committed to increasing both the amount and quality of research in this area. Through September 1999, the National Institute of Allergy and Infectious Diseases (NIAID) held sole responsibility for research in this area. In October 1999, Dr. Harold Varmus, in consultation with Dr. Anthony Fauci, recognizing that a multidisciplinary and integrated approach encompassing the missions of many NIH ICs was necessary to address CFS, incorporated responsibility into the Office of the Director (OD).

Our lab is recognized for our research on a similar gammaretrovirus isolated from nonhuman primates, gibbon ape leukemia virus (GALV). GALV is the only gammaretrovirus other than xmrv found in primates. In collaboration with Frank Ruscetti at the NCI, Bill Switzer at the CDC and Suzan Winfield and Jessica Siegal-Willcot at the National Zoo, we are investigating the source animal for xmrv, and screening gibbon apes in US zoos for the presence of GALV and xmrv.

We have obtained samples from the CDC and the Biological Research Steering Committee that provide us with materials permitting us to determine that many gibbon apes at various zoos have been infected with an xmrv-like virus. We have determined the cell tropism of xmrv using an engineered biologically active xmrv virus with a GFP reporter gene and are identifying cellular factors that restrict xmrv infection of receptor bearing cells.

These factors that can restrict xmrv infection will be used as a means of developing xmrv antiviral drugs. In addition to being a horizontally transmitted infectious agent, xmrv is a threat to the human genome. We are in the process of isolating rat germ line cells and exposing these cells to engineered biologically active xmrv virus with a GFP reporter.

Sperm obtained from these cells are being assessed. Positive results of sperm expressing GFP indicate that xmrv can be transmitted from infected individuals horizontally (i.e., to offspring as a mendelian trait) as well as vertically through the more traditionally route of viral infection. We used cysteine scanning mutagenesis (SCAM) methods to assess the topology of the GALV receptor and intend to identify extracellular domains of the xmrv receptor using similar methods.

These studies will lead to the identification of the xmrv-binding domain.

Finally the spread of most retroviruses is mediated not by direct virus infection but by cell-cell transmission from an infected cell to an uninfected cell. We have developed a model system to assess blocks to cell-cell virus transmission using spinning-disc confocal microscopy to visualized individual budding of fluorescently labeled virus particles into adjacent cells in three dimensional space over time.

More text:
http://projectreporter.nih.gov/project_info_description.cfm?aid=8158079&icde=8151490
 

liquid sky

Senior Member
Messages
371
"In addition to being a horizontally transmitted infectious agent, xmrv is a threat to the human genome."

That just about says it all! So glad to see it in print from a study to be conducted by the NIH. Looking for drugs to treat the infection also.
 

Jemal

Senior Member
Messages
1,031
"In addition to being a horizontally transmitted infectious agent, xmrv is a threat to the human genome."

That just about says it all! So glad to see it in print from a study to be conducted by the NIH. Looking for drugs to treat the infection also.

This is a research project that has been funded with millions of dollars since 2007 by the way. In 2010 they focused a lot on XMRV (before that, just Gibbon Ape Leukemia Virus). There's some bold statements in the 2010 part, quoted above. I think the 2010 part has been completed, but not sure.
 

Cort

Phoenix Rising Founder
Nice catch Jemal.

I agree that the horizontal transmission of XMRV is intriguing and how interesting that primates across the country appear to be infected with an XMRV-like virus.

Positive results of sperm expressing GFP indicate that xmrv can be transmitted from infected individuals horizontally (i.e., to offspring as a mendelian trait) as well as vertically through the more traditionally route of viral infection.
I'm not so sure about piggybacking on CFS for this. There no CFS patients in this study and I don't know that this study should be held up as an example of their commitment to increasing CFS research funding. My guess is that the research community is very interested in XMRV and will continue researching it no matter how it turns out in CFS.

If XMRV works out, though, a study like this is clearly what CFS patients would want to see, though. I imagine its quite expensive.....
 

Jemal

Senior Member
Messages
1,031
I'm not so sure about piggybacking on CFS for this. There no CFS patients in this study and I don't know that this study should be held up as an example of their commitment to increasing CFS research funding. My guess is that the research community is very interested in XMRV and will continue researching it no matter how it turns out in CFS.

If XMRV works out, though, a study like this is clearly what CFS patients would want to see, though. I imagine its quite expensive.....

I agree completely, this study is not focused on CFS. Not even on XMRV (initially). It might yield further evidence XMRV is not contamination though and that is helpful. As I said, there's some bold statements in there... like XMRV being a threat to the human genome. That doesn't sound like laboratory contamination.
 

Jemal

Senior Member
Messages
1,031
The CDC did a study in 1994 by the way looking for several viruses in 21 CFS patients. They also tested for GALV :D

http://www.ncbi.nlm.nih.gov/pubmed/8148438

Anyway, maybe monkeys are the culprit again. They have been looking at mice, while gibbons may have a XMRV like virus. It wouldn't surprise me if it popped up in other animals though. Cats maybe? We'll see how this pans out...
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Interesting project. Switzer is involved. He seems to be taking XMRV very seriously now, and getting really stuck in with complex and advanced research.
 

Rrrr

Senior Member
Messages
1,591
this seems like very big news to me. am i missing something or is this a complete turn around for the cdc, saying xmrv is a threat to the human genome.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
The CDC did a study in 1994 by the way looking for several viruses in 21 CFS patients. They also tested for GALV :D

http://www.ncbi.nlm.nih.gov/pubmed/8148438

Anyway, maybe monkeys are the culprit again. They have been looking at mice, while gibbons may have a XMRV like virus. It wouldn't surprise me if it popped up in other animals though. Cats maybe? We'll see how this pans out...

Hi Jemal, this was debated heavily on some threads last year iirc. XMRV and PMLVs are mammalian viruses. Every mammal could carry it (although some mice are immune), from cats and dogs, to sheep and cattle. We should be looking at getting more research veterinarians interested.

Bye
Alex
 

currer

Senior Member
Messages
1,409
I interpret this paper to suggest that they are concerned about the implications of the XMRV discovery for gene therapy as gammaretroviral vectors are used.

I heard somewhere that HIV had not endogenised yet - that is incorporated itself into the germline.
Maybe they think XMRV might find it easier to do?

This paper is an interesting find.

They also point out that retroviruses usually spread from infected cell to adjacent cells (forming a block of infected cells) and do not travel through the blood. This would mean that tissue samples are more likely to be positive for XMRV than blood. Assuming you got the right tissue that is.

They make it sound as if they know that XMRV can infect the germ cells. If so isn't this very serious?
Can anyone enlarge on this?
As far as I know HIV and HTLV 1 have not done this.
 

Rrrr

Senior Member
Messages
1,591
dr. racaniello gave me permission to post this. -- rrrr
_____


Date: Wed, 18 May 2011 11:36:36 -0400
From: Vincent Racaniello
Subject: Re: is this big news?

This is a progress report for a funded NIH grant, and they are
summarizing what they have done (work on making viral vectors) and
what they plan to do (look for the origin of XMRV). Their statement
'XMRV is a threat to the human genome' appears to be alarming some.
But it's true of any retrovirus - these viruses integrate a DNA copy
of their genetic material into that of the host cell, and therefore
can act as mutagens. This would be a concern if XMRV were indeed
rampant in the human population; but there is no evidence that this is
the case. Plus none of the data have yet been published. Until that
happens, I would not worry about this; it's not big news at all.
---
Vincent Racaniello, PhD
twiv.tv | virology.ws | microbeworld.org/twip | microbeworld.org/twim
| twitter.com/profvrr
'Trust science, not scientists'


On Tue, May 17, 2011 at 9:42 PM,
> professor,
>
> is this nih study big news? it says that xmrv is a threat to the human
> genome. it is an nih funded study. thanks!
>
>http://forums.phoenixrising.me/showthread.php?11716-Interesting-XMRV-research-funded-by-NIH
 

Jemal

Senior Member
Messages
1,031
dr. racaniello gave me permission to post this. -- rrrr
_____


Date: Wed, 18 May 2011 11:36:36 -0400
From: Vincent Racaniello
Subject: Re: is this big news?

This is a progress report for a funded NIH grant, and they are
summarizing what they have done (work on making viral vectors) and
what they plan to do (look for the origin of XMRV). Their statement
'XMRV is a threat to the human genome' appears to be alarming some.
But it's true of any retrovirus - these viruses integrate a DNA copy
of their genetic material into that of the host cell, and therefore
can act as mutagens. This would be a concern if XMRV were indeed
rampant in the human population; but there is no evidence that this is
the case. Plus none of the data have yet been published. Until that
happens, I would not worry about this; it's not big news at all.
---
Vincent Racaniello, PhD
twiv.tv | virology.ws | microbeworld.org/twip | microbeworld.org/twim
| twitter.com/profvrr
'Trust science, not scientists'


On Tue, May 17, 2011 at 9:42 PM,
> professor,
>
> is this nih study big news? it says that xmrv is a threat to the human
> genome. it is an nih funded study. thanks!
>
>http://forums.phoenixrising.me/showthread.php?11716-Interesting-XMRV-research-funded-by-NIH

Thanks for sharing!
It sounds a bit like: "Nothing to see here, move along".

I think there's more to this story. We'll see...
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Thanks for sharing!
It sounds a bit like: "Nothing to see here, move along".

I think there's more to this story. We'll see...

lol, Jemal, that's exactly what I was going to post!

"Nothing to see here, move along..."

The comments do sound like they are trying very hard to make the study sound uninteresting, unimportant and insignificant, don't they!


The study is very interesting, but the words "a threat to the human genome" are probably scientific speak...
It's a fact that if a retrovirus gets into the germline cells, then the virus will be passed to every cell of the offspring, but that doesn't mean that it's a threat to the entire human race.
But at least they are investigating and taking it seriously.
 

ixchelkali

Senior Member
Messages
1,107
Location
Long Beach, CA
Positive results of sperm expressing GFP indicate that XMRV can be transmitted from infected individuals horizontally (i.e., to offspring as a mendelian trait) as well as vertically through the more traditionally route of viral infection.
Isn't this backwards? Isn't traditional person-to-person infection horizontal and transmission to offspring as a Mendelian trait vertical?
 

ixchelkali

Senior Member
Messages
1,107
Location
Long Beach, CA
I don't think the part that says XMRV is a threat to the human genome is a big deal: any human retrovirus is a threat to the human genome, so that's not exactly news. But I think this part would be very cool, if they succeed:
These studies will lead to the identification of the XMRV-binding domain

Also this part:
We have developed a model system to assess blocks to cell-cell virus transmission using spinning-disc confocal microscopy to visualized individual budding of fluorescently labeled virus particles into adjacent cells in three dimensional space over time.


I was surprised when they said that " the spread of most retroviruses is mediated not by direct virus infection but by cell-cell transmission from an infected cell to an uninfected cell"; I didn't know that. Then why is the emphasis in XMRV in ME/CFS on viremia? Is it just because that's what the Lombardi, et al, paper described? Or because they don't know where else to look for it? And if it's in the germ cells, would testing sperm samples find it?

I didn't even know about the gibbon ape leukemia virus. I knew that feline leukemia virus is a gammaretrovirus, and the koala retrovirus, but I don't remember hearing about the gibbons. Poor beasties.
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
I was surprised when they said that " the spread of most retroviruses is mediated not by direct virus infection but by cell-cell transmission from an infected cell to an uninfected cell"; I didn't know that. Then why is the emphasis in XMRV in ME/CFS on viremia? Is it just because that's what the Lombardi, et al, paper described? Or because they don't know where else to look for it? And if it's in the germ cells, would testing sperm samples find it?

It would be nice to think that Judy has been looking for the virus in the tissues, but maybe she's just been trying to perfect her blood techniques.
Looking in tissues would involve lots of technical exploratory work, so I guess only a few dedictated scientists would be interested.

I didn't even know about the gibbon ape leukemia virus. I knew that feline leukemia virus is a gammaretrovirus, and the koala retrovirus, but I don't remember hearing about the gibbons. Poor beasties.

This is interesting, from Hillary Johnson's website:

The agency tried to replicate DeFreitas findings and failed. Nevermind that scientists in Atlanta refused to follow DeFreitas exacting protocols, worked out over a period of four years; or that the blood samples the agency was using became contaminated with a gibbon ape leukemia virus during the experiments; or that the number two at the agency, the deputy director, shut the investigation down with a, Thats it boys and girls, before the agency scientists involved believed they had had a chance to explore the finding fully.

http://www.oslersweb.com/the_why___a_speech_in_london_86981.htm

So was this contamination or had they actually detected a virus similar to XMRV?

It's an interesting thought.
 

ukxmrv

Senior Member
Messages
4,413
Location
London
ixchelkali, Dr Mikovits said something like that at the IiME conference. She was talking about dendritic cells in HTLV and that infection was direct from cell to cell (well at least I think that is what she was saying).