XMRV: Not in spooge

Lack of Detection of XMRV in Seminal Plasma from HIV-1 Infected Men in The Netherlands

These folks looked in the semen of HIV-1(+) men for XMRV-- because of XMRVs association with prostate cancer, and retroviruses as STDs, and because HIV+ people are more susceptible to infections than HIV- people.

29 homosexual men (not on any antiretrovirals), 25 heterosexual men (most, not all on antiretrovirals)-- no XMRV in 93 semen samples. Even though some of the men were on antiretrovirals, the number shouldnt have been zero. They had a built in control: HIV-1. HIV-1 was found in most of the homosexual mens semen (not on any antiretrovirals) and few of the homosexual men (result of most of them being on antiretrovirals). And, there is currently no evidence any currently approved antiretroviral used for HIV-1 treatment has any effect on XMRV 'infected' persons, much less the specific drugs that these men were taking.

But why didnt these scientists look for XMRV in PBMC or blood or something else too? I mean, why did the scientists even assume that any of these people were XMRV positive?

Well, we have no diagnostic test for XMRV. Its not in the blood of 'infected' humans. 'Infected' humans do not reliably have antibodies to XMRV, apparently. And if XMRV is hiding in lymph nodes or prostate tissue or something, those areas arent exactly conducive to basic diagnostic sampling. And, apparently the only people who can detect XMRV in PBMCs using PCR are the WPI and 500-year-old voodoo priests.

All scientists can do at this point is sample a population that would be extremely likely to be infected with XMRV, if it exists: HIV-1 positive men.

All scientists can do is to comb through their semen, looking for XMRV. Its either there, or it isnt.

It wasnt.

While this is extremely important for figuring out the epidemiology of XMRV, all I can think is, "Thank god our spooge supply is safe."

*solemn-nod*

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What did 500 year old voodoo priests ever do to you?

By Prometheus (not verified) on 12 Aug 2010 #permalink

You don't think you get to drink Mountain Dew and keep those abs without some exceptionally talented help?

I'm not sure how "safe" you should consider HIV infected splooge! As a straight male I pick other health drinks, however each to his, or her, own.

SWH-- You didnt get the memo: "CFS is worse than AIDS", you see, so as long as sperm is XMRV free, its okay.

:-S

If you're worried about (retro)viruses in your spooge, you need to cook it longer.

Or use more booze in your mixed drinks.

XMRV: Not in spooge - top contender for the Best Post Title short-list!

Perhaps all us men should send a sample of our spooge to the WPI for confirmation.

Something I don't get: what difference did their sexual preference make in this study? They were all HIV+ right? I can see where they might want to separate those individuals who became infected with HIV through IV drug use (or transfusion) if they're trying to delineate whether the virus was sexually transmitted. But why separate the gay men from the straight men in the study? (Were they looking for the magic Gay Virus?) Is there some assumption there that the gay guys are/were mostly having anal sex and the straight guys are/were mostly having vaginal sex? Let's say they did find virus and it was mostly in one group vs. the other. What conclusion would you draw?

Saw this recently, and found another one in Retrovirology while trying to find it again.

http://journals.lww.com/aidsonline/abstract/2010/07170/Absence_of_xenot…

Absence of xenotropic murine leukemia virus-related virus in blood cells of men at risk for and infected with HIV

Kunstman, Kevin J; Bhattacharya, Tanmoy; Flaherty, John; Phair, John P; Wolinsky, Steven M
AIDS. 24(11):1784-1785, July 17, 2010.
doi: 10.1097/QAD.0b013e32833b76fb

Xenotropic murine leukemia virus-related virus has been detected in blood cells of patients with chronic fatigue syndrome and in 3.7% of healthy controls from the same geographic region. We evaluated 996 men who were participants in the Multicenter AIDS Cohort Study for xenotropic murine leukemia virus-related virus sequences in blood cells by means of a real-time quantitative PCR assay. Xenotropic murine leukemia virus-related virus was detected in none of the men on the basis of the absence of xenotropic murine leukemia virus-related virus DNA, suggesting that infection may be population-specific.

http://www.retrovirology.com/content/7/1/63

No evidence for XMRV association in pediatric idiopathic diseases in France

"None of the 152 pediatric samples (72 various idiopathic diseases and 80 respiratory diseases) and the 19 SpA samples tested was positive for XMRV (Figure 1C) or related env sequence, since our primers also allowed us to detect both xeno-MLV and polytropic MLV [25,26].

In contrast with our results on pediatrics respiratory disease samples (bronchiolitis and others), Fischer et al. found a significant proportion of XMRV gag sequences in all of their respiratory disease patient and donor groups (between 2 to 10%). They found the highest incidence of gag XMRV detection in the group of immunosuppressed patients (adults conditioned before transplant) [27]. Although, this confirms that XMRV is more likely to emerge in the context of altered immune response, it remains perplexing that no other report found XMRV in Europe."

By Richard Jefferys (not verified) on 13 Aug 2010 #permalink

If I were designing the study, I would have at least cross-checked all those spooge patients with with a co-test of their respiratory tract samples. How hard would that have been?

Didn't somebody else find 9-10% XMRV positive in immuno-compromised patients using respiratory tract secretions? And what, 3-5 percent in healthy controls or something. When I go fishing, I usually throw my line in where the fish are. But then, I am not a scientist.

@Levi #10
If you read the paper, you'll see that the 996 XMRV-negative spooge samples were collected anonymously, so no chance of also getting these men to cough into a tube.

Getting 1,000 other people to cough into a tube is a different matter, requiring IRB approval of the study and all that.

The questions are many: What is the epidemiology of XMRV? Does it spread by sex, or by casual contact? Does it really exist at all, or is some type of PCR contamination a more likely explanation for the observed positives? Do people who handle wild mice or lab mice face increased risk? How did it get from mice to humans?

Dr.Duke,

Many thanks for your comments. Right, I read all that about the anomymous source of the spooge and ethical considerations, etc. for the particular patient population of this study. Here is where my non-scientist perspective and leanings come in.

I mean, how hard is it to collect spooge samples for testing? It looks like the study was designed around the available samples (hmmm, lets find a hypothosis for these darn AIDS spooge samples we have lying around . . .XMRV is hot right now. THAT might be easy to publish). Is that really how it works?

Don't AIDS researchers connect with needle exchange programs or simlar folks in the loop to get a free and unending supply of anonymous AIDS blood, snot, or spooge as needed for such studies? I am probably naive about the difficulties in arranging patient populations for study and the ethical no no's.

Here is a link with info on the XMRV respiratory tract work.
http://www.virology.ws/2010/05/19/xmrv-in-human-respiratory-tract/

cynical1-- The homosexual/heterosexual thing is just a side-effect of their sampling. These people were enrolled in other studies for something else entirely (the heterosexual men were on antiretrovirals, because they were assessing sperm 'quality' on antiretrovirals, for HIV+ men trying to have a baby with their wife/girlfriends). Cohorts are hard to get. If you get one set up and get samples of X/Y/Z, you use every damn bit of those samples to get as much info as you can.

One of my main projects, I was literally scraping the bottom of cryotubes trying to get one more experiment out of samples that are impossible to get anymore.

Scientists use every part of the buffalo.

Richard-- *hat-tip*

SSB-- I (almost) totally agree with Racaniellos points. The experiments he proposes would have been neat. But I have no problem with the protocols or conclusions in this paper.

The data in this paper supports their assertion that there is no XMRV (aka cell free XMRV) in in seminal plasma from HIV-1 infected men, in their cohort. Free virus is not in seminal plasma. Thats the title of the paper. Not 'XMRV is not found in semen'.

It is absolutely true that cells in sperm could be a source of XMRV transmission. This is a way HIV-1 can be spread. Its not the sperm thats infected (retroviruses dont want to be in sperm, its a mistake and a dead-end to replication (see blog title)). But immune cells can get into semen, and they could be infected with something, and they could transmit said something to the sexual partner. However, that was not the question of this paper. They didnt say XMRV wasnt in cells in semen. Thats a separate question they could have asked, but again, not the title of this paper.

It is illogical that people can find free XMRV in immunocomprimised individuals lung juice (no PBMC tested), but not in sperm (see Levis comment). Im glad these scientists reported this finding.

Levi-- Its not just spitting into a cup. To obtain bronchial lavages, you literally wash out peoples lungs with about half a liter of saline. You also have to go under for the procedure. It would have been very, very hard to convince these people to submit to that for no personal medical reason, and I doubt it would have been IRB approved for this reason (this can be a life threatening procedure, with no medical benefit or necessary to the patient).

Also, looking for free XMRV in lungs is stupid. It is literally the last place in a human I would look for cell-free XMRV. I would look in spinal fluid and brains before I would look in lung juice, for this virus. I dont believe that paper, at all, and even if you do, its beyond bizarre that XMRV is in fucking bronchial lavages and not sperm.

This story really extends far beyond XMRV, into the other viruses that also have no epidemiology, or serology, to back up the PCR findings. For example the "Human Mammary Tumor Virus" that is 99% to 100% identical to lab strains of mouse mammary tumor virus. Or the "HIV-like Human Cancer Virus" of Eva Rakowicz-Szulczynska (http://www.virotech.us/page/page/5376350.htm ).

PCR is very powerful, but it is also very prone to problems. Using "negative controls" is not necessarily a guarantee that nothing has gone wrong anywhere along the way. Were the "negative controls" taken through every step of DNA or RNA extraction purification? Or are they only blank water samples added at the last step when the real samples have patient DNA or RNA added?

The simple way to solve this conundrum once and for all is to have 3 or 4 labs all test a panel of double blinded samples, negative and positive controls. That experiment is reportedly underway, but in the mean time dozens of conflicting studies continue to add fuel to the fire.

Yes, that study is underway.

And 100% of the samples are being collected by Judy.

Guess how I feel about that.

ERV states: "Yes, that study is underway. And 100% of the samples are being collected by Judy.Guess how I feel about that."

Well, two separate recent zero/zero XMRV studies used samples collected by psychiatrists Bill Reeves and Simon Wessely. Those guys have their reputations at stake for long histories of publishing articles that say CFS patients are victims of child abuse and have personality disorders but no organic illness of any kind.

They collected (and handled) the blood and given to the virologists. CFS folks were completely dismayed. But you yourself said on this website that there are laws against tampering with experiments and the truth would finally come come out in the end. Or something that that.

I am para-phrasing your response to questions last winter about the possibility that Wessely might have snuck some of his pet labrador blood into the vials and given them to Dr. McClure. You had some outstanding thoughts about the theory of using cloned sterile pig blood instead.

So, if she was inclined, what would Dr. Judy need to do in order defeat a double blind XMRV study with negative and positive controls?

DrDuke: "If you read the paper, you'll see that the 996 XMRV-negative spooge samples were collected anonymously, "

Glory Hole Science!?

I do not see a real problem with Mikovits collecting the samples. If the same CDC arrays (that could not produce a single positive result) suddenly produce positive results, I'm sure things will be figured out.

ERV, I'm interested in your take on this:
http://www.cfids.org/xmrv/default.asp (scroll down to the last paragraph before the "coming up" header). A (small but readable) slide of the actual results: http://www.cfids.org/images/2010/xmrv-blood-panel.jpg

It seems the CDC performed remarkably well on sensitivity AND specificity with "spiked" samples. The WPI was the only lab to report an unexplained false positive. My question: Is such a test an indication of the expected quality of results with 'true' (i.e. positive human) samples? Or are these results virtually meaningless? How was (or is) this with HIV (spiked vs human) samples?

You all should read DR Bells faces of cfs book describing 10 cfs patients he diagnosed. Google bell cfs to get a link to his site and the book pdf.

How do people get xmrv in theyr jizz anyways?

Levi: Mikovits wouldn't have to do anything deliberate/malicious. She could just have a lab that is riddled with murine-leukaemia virus contaminants. It has happened to labs in the past, labs of very prominent scientists. Some virologists get worried if they spot a new virus, because while it might mean they've found a new human pathogen, it might also mean their lab is screwed and needs sterilising (making a dirty lab sterile again? Very, VERY hard). Whereas Wessely would have to have actively tested lots of blood samples, picked the XMRV-free ones, and then substituted them for any potentially infected ones. Of course, like most of the other labs in Europe who haven't seen signs of XMRV (who maybe aren't getting samples (cell lines that are just shedding XMRV EVERYWHERE) unlike US labs who may have collaborators sending samples from the WPI and NIH...), it's possible the UK and European studies aren't seeing XMRV because it's really not here.

If there's a cover-up going on, no one told me :(

[off the current topic, but related to a previous post]

Hi "ERV" ;-)

A while back you mentioned being interested in the quasispecies concept. You might like these posts from Ian York's Mystery Rays in Outer Space (crazy name, but a "serious science" blog):

http://www.iayork.com/MysteryRays/2010/07/26/quasispecies-thoughts/

and "just out":

http://www.iayork.com/MysteryRays/2010/08/10/dna-virus-quasispecies-pro…

While I'm writing, the local news my way (in NZ) is that a local climate change denial group has gotten the bright (read: daft) idea of taking the government met service to court because they don't like their temperature data. Sigh

"Scientists use every part of the buffalo."

Bwahahaha!

"Smart women are *so* hot!" -- Xander Harris.

"Well, we have no diagnostic test for XMRV. Its not in the blood of 'infected' humans. "

We have no official test, but what do you mean by the second part?

No one has found cell-free virus in blood of 'infected' humans. I havent seen that published anywhere, including the Mikovits paper.

The only people who have found cell-free virus anywhere is the German group, who found XMRV in bronchial lavages (points to the comments above).

It's been out a whole hour - and no comments on the positive Alter paper? Come on people - this is the internet age.

http://www.pnas.org/content/early/2010/08/16/1006901107.full.pdf+html

Small samples, not entirely clear how patients were selected, but it surely it now looks likely that the WPI's work is going to lead on to something important.

I'm rather surprised. If a significant portion of CFS patients are ill because of a viral infection, then the way that they have been treated is scandalous.

That paper doesnt say what you think it says.

They didnt find XMRV.

They found endogenous mouse retroviruses.

This entire field is fucking insane.

@ ERV - So now you can read minds? Please feel free to go on about what you think I think...

I didn't say one word about XMRV. I was just cautioning that next time you might want to be a bit more careful (and a lot less arogant) before you swallow (the notion that you're beyond learning somehting new).

Check out the lead author of the paper: Shyh-Ching Lo! Did cooler ever post here about his mycoplasma theory of AIDS or was that just on Aetiology? Maybe it's a different Shyh-Ching Lo?

By Richard Jefferys (not verified) on 23 Aug 2010 #permalink

Are there two Shyh-Ching Los that studied mycoplasma in the 90s? Looks like the same guy. And yeah cooler came here last spring IIRC. Funny how Lo never claimed TMK that mycoplasmas caused AIDS - that was just something cooler came up with himself (or got from another source).

'S'-- I 'know what youre thinking' because I can read every post youve posted here before under different handles.

XMRV is not in spooge, according to the paper in the OP, and according to the paper you posted. Absolutely nothing in that paper you posted 'validates' anything Mikovits published. The paper you posted is fantastic crap, and if you can wait 10 minutes for me to take a shower after boxing, you will know exactly why.

:-D

Really sad. It's AIDS denial in reverse.

http://www.nytimes.com/2010/08/24/health/research/24fatigue.html

"'I think it settles the issue of whether the initial report was real or not,' said K. Kimberly McCleary, president of the CFIDS Association of America, the leading organization for people with chronic fatigue syndrome."

By Richard Jefferys (not verified) on 23 Aug 2010 #permalink