Transplant Experts share XMRV transmission concerns: Retrovirology journal

[parvofighter]

Serious-minded scientists at the journal Retrovirology are asking important "What if" questions about XMRV. (Seems they are undeterred by Groom et al's failure to find XMRV in the UK). This latest concern about XMRV comes from the organ/tissue transplant area, where they are expressing very real concerns about XMRV, AND are pushing for testing for, and further research into XMRV.

Summary of the following abstract:

1. There is a shortage of human tissue/organ material for transplants
2. Porcine (pig) transplants are one way to address this shortage
3. Pig transplants can contain PERV's (I know, I know), or Porcine Endogenous Retroviruses.
4. PERVS are known to combine synergistically with other human viruses (much like alcohol can powerfully combine with drugs in college students), which in turn can be disease-producing.
5. PERVS are similar to XMRV, and the PERV industry doesn't want their tissues/organs to be rejected if they are mistaken to be contaminated with XMRV
6. Organ/tissue transplant recipients will need to be tested for XMRV to prevent the possibility of XMRV recombining with PERVS to produce a new virus that could affect the transplant/tissue acceptance.

Bottom line, the transplantation industry is HUGE, and its financial interests -as well as positive clinical outcomes - could be affected by XMRV in two ways:

• If XMRV itself is proven to be pathogenic (and based on the CROI Conference on Retroviral Infection results - see thread http://www.forums.aboutmecfs.org/showthread.php?3241-HOT!-Coffin-Sharma-and-Goff-Conference-on-Retroviral-Infections...&highlight=croi- we're heading in that direction)
  
• If XMRV, in recombination with a porcine endogenous retrovirus (PERV), creates a new, disease-causing virus in tissue/organ transplant recipients.

From: http://www.retrovirology.com/content/7/1/16

Commentary
Detection of a gammaretrovirus, XMRV, in the human population: Open questions and implications for xenotransplantation

Joachim Denner

Retrovirology 2010, 7:16doi:10.1186/1742-4690-7-16

Published: 10 March 2010 Abstract (provisional)

XMRV (xenotropic murine leukaemia virus-related virus) is a gammaretrovirus that has been detected in human patients with prostate carcinoma, chronic fatigue syndrome (CFS) and also in a small percentage of clinically healthy individuals. It is not yet clear whether the distribution of this virus is primarily limited to the USA or whether it is causally associated with human disease. If future investigations confirm a broad distribution of XMRV and its association with disease, this would have an impact on xenotransplantation of porcine tissues and organs. Xenotransplantation is currently being developed to compensate for the increasing shortage of human material for the treatment of tissue and organ failure but could result in the transmission of porcine pathogens. Maintenance of pathogen-free donor animals will dramatically reduce this risk, but some of the porcine endogenous retroviruses (PERVs) found in the genome of all pigs, can produce infectious virus and infect cultured human cells. PERVs are closely related to XMRV so it is critical to develop tests that discriminate between them. Since recombination can occur between viruses, and recombinants can exhibit synergism, recipients should be tested for XMRV before xenotransplantation.

​

In other words, we have another powerful stakeholder group fighting for good science, and a better understanding of XMRV. :Retro smile:

 

[parvofighter]

"Important questions remain to be answered" (about XMRV): Retrovirology

For more "meat" on the above abstract: Here are some excerpts from the provisional Pdf, available from: http://www.retrovirology.com/content/pdf/1742-4690-7-16.pdf

Love how this author brushes aside (indeed ignores?) the cobwebs of CBT/GET politics and media manipulation, to get at core scientific questions on XMRV:

"Important questions remain to be answered:

• How and when did this murine xenotropic virus infect humans?
• Is it a direct infection from rodents to susceptible humans or is the virus spreading through human populations resulting in high virus load in (immunosuppressed) tumours and CFS patients?
• Is a third species transmitting the virus from mice to humans?
• As mentioned above, 3.7 % of healthy controls from one study in the USA were virus positive (3). Why is the virus common in the USA but rare in Europe?
• Are there specific populations of rodents in the USA releasing this virus? Why is disease associated with XMRV in the USA but not in Europe?
• Is XMRV a passenger virus replicating in immuno-compromised individuals or does this virus contribute directly to disease progression? (Note: Thanks to the recent hot Schlecht-Louf French study on XMRV's ability to suppress patient's immune systems due to an envelope-mediated factor, we know XMRV has pathogenic potential.)
• The immunosuppressive properties characteristic of all retroviruses (15) could contribute to tumour progression as well as to the symptoms of CSF. If XMRV is indeed widely distributed in the human population and associated with tumours and CSF, should blood donors be tested in order to avoid XMRV transmission?"

"With so many unanswered questions, much work remains to be done. At this early point in XMRV research, areas should be identified in which this virus may cause a serious impact on human health."

(Note: Proof of XMRV being causal for either prostate cancer and/or ME/CFS is the trigger that will drive these scientists into hyper-speed. This intense interest in XMRV, as illustrated in this article, is GREAT for us. We want these answers too, but now we're not fighting alone!:Retro wink
​

"One of these areas may be the xenotransplantation of porcine tissues and organs to humans. If XMRV is indeed circulating in the human population, it has important implications for xenotransplantation. A test should be developed to discriminate between PERV and XMRV, and the potential for recombination between the two viruses should be investigated."

​

 

[MEKoan]

Pub date Mar. 10! Somebody better tell these retrovirologists that this whole thing is an inconsequential delusion on the part of people with abnormal viral beliefs!

So, Parvo, I have to admit that the very first thing that sprang to this vegetarian's mind when I read, "In other words, we have another powerful stakeholder group fighting for good science, and a better understanding of XMRV." was: Yeah, the poor wee pigs!

(You should hear the lovely sound my new keys make when I tap them. It's like music.)

Ok, sorry, this is a serious and very hopeful development for all of us... and the pigs, too.

Peace out,
Koan

 

[parvofighter]

Thanks ladybugmandy!

ladybugmandy, have you checked out the size of my nose in my avatar? That's how!:Retro smile:

 

[Abraxas]

Thanks Parvo for another great post :Retro smile:

 

[Athene]

Parvofighter you are one of our heros! You put up so many posts that give me real hope...
Thank you again.
xxx

 

[parvofighter]

Another reason Porcine tissue transplants are at risk in presence of XMRV

Thanks for the kind feedback!:Retro smile: Just trying to build a win/win for our team beyond our disenfranchised ME/CFS patient population... we need some heavy hitters to speed up XMRV research!

XMRV + immunosuppressive therapy = a BIG problem for the transplant industry
Here's another reason why the organ/tissue transplant industry should be concerned about XMRV in recipients: the need for immunosuppressive drugs to minimize risk of transplant rejection. How many of us could tolerate additional immunosuppression? In other words, I believe the problem isn't only all those PERV's Retro tongue, and the possibility of recombination with XMRV as outlined above, but the fact that for any transplant, the recipient needs to take immunosuppressive therapy.

From: http://koreamed.org/SearchBasic.php?RID=533673&DT=1&QY="Infect+Chemother"+[JTI]++AND+2010+[DPY]
Infection Chemotherapy. 2010 Feb;42(1):12-16. English.

Detection of Human Cytomegalovirus (HCMV) and Porcine Endogenous Retrovirus (PERV) with One Step Extraction Method.

Kim JH, Jung ES, Hwang ES.

Departments of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Korea. hesss@snu.ac.kr BK21 Division of Human Life Science, Seoul National University College of Medicine, Seoul, Korea. Institute of Endemic Disease, Seoul National University Medical Research Center, Seoul, Korea.

BACKGROUND: Xenotransplantation is thought to be one of the alternative methods to overcome the shortage of human organs for transplantation. Recipients should be immunosuppressed for graft survival, and thus, there is a need for developing diagnostic modality that can detect diverse infections originating from animals and recipients rapidly, in the early stage, and with high sensitivity using small volume of samples. This study was carried out to develop a fast, simple, and robust technique for the preparation of HCMV DNA and PERV RNA using small volume of samples. MATERIALS AND METHODS: Nucleic acids were extracted from serially diluted samples with one step extraction method as well as with Qiagen kit. The presence of genomic DNA of human cytomegalovirus (HCMV) and porcine endogenous retrovirus (PERV) was detected by PCR and specific primer set, respectively. RNA of HCMV and PERV was extracted and then detected by RT-PCR and specific primer set, respectively. For absolute quantification of HCMV, standard curve was established by real time PCR. RESULTS: HCMV DNA and PERV RNA were prepared from culture supernatant and cells for PCR or RT-PCR with one step extraction method. It was possible to extract both the DNA and RNA from the samples in about 20 minutes with one step extraction method in a single tube. HCMV and PERV could also be detected by PCR and one step extraction method, respectively. It was also good with small quantity samples. CONCLUSIONS: One step extraction method is simpler and faster method than other extraction methods when there are two types of DNA and RNA viruses in one sample. From these results, we could see that the one step extraction method could be very useful in detecting HCMV and PERV rapidly from the pig cells or organ transplanted recipients with a small amount of sample.
​

In summary, the XMRV party is getting inevitably bigger. The transplant industry will very likely be a strong ally in our quest for rapid, reliable XMRV diagnostics - and of course treatment as indicated. They've got a lot riding on XMRV too - even if the whole industry doesn't realize it yet.

 

[sproggle]

:victory::victory: Great find Parvo!! :victory::victory:

 

[MEKoan]

Dear Parvo,

I may well be the only one but I can't read your fantastic posts because of both the density and the colours. I really don't want to be a whiney nuisance but I have a feeling that what you are posting is super interesting and I would love to be able to read it. I think I could cope better with the colours if the blocks of text were broken up. And, probably visa-versa but not sure about that.

 

[Daisymay]

Very interesting Parvo thanks v much. May your info be reposted on other ME/CFS lists?

If not quite understand.

Thankls for all your work on this.

 

[starryeyes]

Thanks for posting this Parvo. You do dig up the some of the best info on CFS and XMRV! :sofa:

 

[parvofighter]

Sure, I'll try; yes; and thanks!

Hi Koan,

Thanks for the feedback. I'll try to break things up in my next posts - let me know if that helps. I admit I'm a tad addicted to formatting... and folks seem to like to like it as they can quickly skim the subtitles of my posts, and decide for themselves if they want to read more. That said, there are probably a few things I can do to help you in my future posts .... let me know how it goes.

You should also try to fiddle @ your end, and I'm guessing Apple Help may have the answer. Something that might help ... and I'm speaking as a PC, rather than Mac user, so it will be a bit different on my system:

If you want to get rid of the high contrast stuff, there should be a setting that you can change on your Mac. On my PC, this is what I do:

Click on Start
Go to Settings
Then Control Panel
Then Appearance and Themes
Click on High Contrast
Click on Settings
Click Rainy Day (there are many different options - on my PC, Rainy Day is the least gaudy!)
Click OK
Click Use High Contrast
Click Apply
​

And Presto - most of the colors are GONE! Looks just like they call it - Rainy Day. This approach might make the puter easier for you in general. I suspect Apple Help might have several things you can do to change the contrast, colors, intensity, etc.

Other Mac users - do you have any suggestions to help us out?
​

May your info be reposted on other ME/CFS lists?

@ dasiymay, Yes, absolutely. My only request is that you give attribution. The easiest way to do this is just type in "From:" before the quote from this site, and copy/past the URL (the web address at the very top of your navigation bar), so that readers can click on the source to directly find the website (Cort's forum), the discussion thread, and the writer. No need to write in Parvofighter.

And @ teejay - thanks again!:Retro smile: I like digging.

 

[Michelle]

Parvofighter --

Also want to add my thanks for this and all the great stuff you find to keep our hopes up.

I had a question regarding this comment/question you asked:

# Is it a direct infection from rodents to susceptible humans or is the virus spreading through human populations resulting in high virus load in (immunosuppressed) tumours and CFS patients?

Do you mean humans might be getting XMRV directly from mice and not from other human beings? My brain is fuzzy a lot so I might be completely misreading you there. But in light of the discussion a couple of us were having in an earlier thread about a connection to rodents/pets/fleas, I wondered if that actually was a real issue or just some of the endless conjecture we all do because there's so few answers/good research.

Thanks again.

 

[parvofighter]

Hi Michelle

Hi Michelle,

And thanks for your question.:Retro smile:

I had a question regarding this comment/question you asked: Do you mean humans might be getting XMRV directly from mice and not from other human beings?

Unfortunately I can't take credit for the question - it was one of several posed in the .pdf document: http://www.retrovirology.com/content...-4690-7-16.pdf, that I quoted in my Post #2 in this thread. I just put them into bullet form for easier reading.

But this IS a question that many retrovirologists seem to be asking... is XMRV repeatedly
jumping from mice to humans, or was there one unique interspecies "jump",
that has since been transmitted between humans?
​

It's nice to see the author of this transplantation paper asking it too. I'm combing my memory on this - if I recall correctly, John Coffin has openly mused on this in his testimony at the 2009 CFSAC meeting, as well as in the proceedings/videos of the 2010 Conference on Retroviral and Opportunistic Infections. What I've been able to glean so far is that the jury is still out on this, and may be for some time.

The lack of genetic variability within XMRV strains however (I think it was 6 nucleotides??), even given XMRV's SLOW replication rate, would suggest that the jump or jumps have been relatively recent - whatever that means (Coffon speculated 40 years, I recall)!

And would this narrow nucleotide variation with XMRV in humans (eg. the 2 prostate cancer strains & the CFS strain of XMRV) allow for MULTIPLE jumps from mouse to humans - or was it just a massive confluence of circumstances that allowed just a single jump? Instinct might indicate that if it were happening repeatedly from mice to humans, that each jump might result in subtly different nucleotide changes... would they still have such a narrow band of variation? My sense is that the retrovirologists are just as puzzled as we are, given XMRV's slow replication rate, and the early stage of this research... and that it will take some more time until this question is answered.

But now I want to take a look @ your rodent/pet/flea thread, because it's so well grounded in history. After all, the worst plague - literally The Plague - was the result of rodent/flea/human interaction, wasn't it? If that were the case however, parts of Canada (where I live) are literally devoid of fleas (smart things), likely due to our prohibitively cold climate in some (OK, most:Retro smile regions. I wonder if the ME/CFS/prostate cancer epidemiology would parallel the distribution of fleas? Is there such thing as a "flea map"? And when the ME/CFS researchers and epidemiologists get the funding, I wonder if they might look to see if there's a parallel between ME/CFS and flea etc. distribution?

Not sure if this helped you Michelle - it's a really interesting discussion, and thanks again for bringing it up. Anyone able to add some meat to my wild guesses?:Retro smile:

 

[noddyboddy]

Serious-minded scientists at the journal Retrovirology are asking important "What if" questions about XMRV. (Seems they are undeterred by Groom et al's failure to find XMRV in the UK).

People keep saying that Groom et al didn't find XMRV in the UK. That's WRONG. They DID find it... just not where they expected.

They found it in their healthy controls and not in CFS patients. This is important! 1) It shows that XMRV is in the UK -- and contradicts McClure, Wessly, et al, who claim that it isn't. 2) The fact that they found it in healthy people suggests the background rate of XMRV in the UK is 1% -- compatible with other studies ranging from 1-6% background rate. 3) Since they found it in healthy people, not CFS patients, this is evidence that the UK patient cohort is different than the WPI patient cohort.

Instead of focussing on the 'negative' aspect we need to focus on the fact that this study, for the FIRST TIME in Europe, actually found XMRV! Naysayers can't say, "It's not in Europe" any more. It IS in Europe. That has profound implications.

 

[noddyboddy]

Btw, Dr. Judy has already addressed the rodent thing.

No, it's NOT a mouse virus. It's a human virus. It's xenotropic, meaning it cannot cause disease in mice. XMRV differs from the viruses carried by wild mice. At some point in history, it changed in a way to infects humans but not mice. Now human beings are the disease vector, not mice.

If you read the transcript of the question and answer sessions she had online a few weeks ago, the information is in there.

 

[parvofighter]

Thanks NB!

People keep saying that Groom et al didn't find XMRV in the UK. That's WRONG. They DID find it... just not where they expected. They found it in their healthy controls and not in CFS patients. This is important!

...Naysayers can't say, "It's not in Europe" any more. It IS in Europe. That has profound implications.

You're right - I stand corrected. That's a critical distinction.

 

[julius]

Keep posting noddyboddy....that's some good stuff