How XMRV, the new human retrovirus associated with prostate cancer and chronic fatigue syndrome, might be transmitted among humans is unknown. The finding that the virus can be detected in prostate cancer cells, and in prostatic secretions of men with prostate cancer suggests that it could be sexually transmitted. To address this question, the presence of XMRV in seminal plasma of men with HIV-1 was examined. Although the virus was not detected in 93 samples from 54 HIV-1 infected men, the study provides little information on possible transmission mechanisms of XMRV.
This study involved two groups of HIV-1 infected men from the Netherlands: 29 who have sex with men, and 25 heterosexual men. The rationale for examining HIV-1 infected men for XMRV was that “they have a higher chance of contracting sexually transmitted pathogens than non-HIV-1 infected men”. For 39 men a second sample was also available from another time point, bringing the total samples to 93.
To detect XMRV, semen samples were diluted 1:1 with buffer and centrifuged to remove cells, yielding seminal plasma. Total nucleic acid was then extracted and subjected to reverse-transcription and then polymerase chain reaction. This procedure assays for the presence of XMRV viral RNA. At the same time, the samples were also tested for the presence of HIV-1 RNA. The positive control for XMRV was total nucleic acid extracted from a prostate cancer cell line known to produce viral RNA.
The results show that HIV-1 was detected in 25% of the seminal plasma samples, while none contained XMRV nucleic acid. The authors conclude:
Although HIV-1 was amplified from 25% of the seminal plasma samples, no XMRV was detected, suggesting that either the prevalence of XMRV is very low in The Netherlands, or that XMRV is not naturally present in the seminal plasma.
In my opinion, these conclusions are not supported by the data obtained in this study. Here are my reasons:
- The semen samples were subjected to centrifugation, which removes all cells, including spermatozoa, epithelial cells, and lymphocytes. Such cells could harbor virions.
- The study was designed only to search for XMRV virions or viral RNA, not proviral DNA, which is integrated into cellular DNA.
- No attempt was made to determine if the 54 men were infected with XMRV. This could have been done by taking blood samples and co-culturing them with LNCaP cells, then performing PCR. If none of the men were infected with the virus, then absence of the virus in their semen is meaningless.
To determine if XMRV could be transmitted in semen, I would obtain semen samples from patients known to be infected with the virus. Then I would co-culture total semen and seminal plasma with LNCaP cells to amplify any virus present, followed by PCR to detect either virions or proviral DNA. I realize it may be difficult to conduct the study in this way, but I don’t see the value of doing it any other way.
Marion Cornelissen, Fokla Zorgdrager, Petra Blom, Suzanne Jurriaans, Sjoerd Repping, Elisabeth van Leeuwen, Margreet Bakker, Ben Berkhout, & Antoinette C. van der Kuyl (2010). Lack of Detection of XMRV in Seminal Plasma from HIV-1 Infected Men in The Netherlands PLoS One : 10.1371/journal.pone.0012040
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I think we're going to see a lot of this sort of thing in the coming months. XMRV is red-hot right now, so everyone who has access to patient samples of any type will probably be tempted to test for this virus. Whether the results are positive, negative, or meaningless, they can get a quick publication that will probably attract at least a few citations and maybe even some media interest.
Thank you for this review on this paper.
I get concerned when they can't find any XMRV at all, which makes me question whether they used a proper technique.
I would love to see you having a podcast with Dr Judy Mikovits. I think it could help the scientific community understanding CFS and XMRV. Thanks, Kati
Thank you for your sharp analysis of this paper, Professor.
Thanks you for the illuminating analysis.
Thank you for the thorough analysis of this paper. As Alan Dove points out there will be many studies hoping to capitalize on the interest in XMRV. And sadly many scoring at home, often to include the media, count all papers with equal weight and just tally an effort like this as a negative study.
Your efforts to call them as you see them is greatly appreciated to shed some light for those wishing to look more deeply into the science.
By now, researchers who are paying attention should have figured out that PCR alone is not sufficient for detecting XMRV. If they are doing PCR alone, they may as well just throw out their results and their careers with it. Seriously.
Thank you! That's just what I said when I read this. Now that you say the same thing, I know it's not just that I'm a dumb layman and it was over my head. Oooo, I feel so smart; it must come from listening to TWIV.
One thing I've noticed is that just because someone is a highly educated, experienced scientist, doesn't mean they're logical. The lack of logic is some science papers drives me nuts, especially the giant leaps of logic between evidence and conclusion.
I second that Dr. Mikovits should be asked to do a broadcast along with Dr. Singh. Dr. Mikovits was the first person to isolate virus from PBMC's of CFS patients. I think your broadcast is fascinating I would love to hear what she has to say. I also think she should have a plenary talk at the 1st ever XMRV conference but that's just my opinion
Very interesting dissertation thanks
Thankyou Prof. Racaniello.
I'm pleased to see poor science being labelled what it is.
I was certainly unimpressed by research which was attempting to find evidence of a retrovirus in a cohort of men, nearly half of whom were already taking anti-retroviral drugs.
Is this a relevant consideration ?
Are research papers that are published on PLos One to be taken seriously? Are they adequately peer reviewed?
Perhaps the important errors that you have pointed out in this research paper could have been ironed out prior to publication if they had been submitted to a more respectable publisher of science papers?
Yes we would like to see Dr Mikovits on your podcast soon.
Yes we would like to see Dr Mikovits on your podcast soon.
You are spot-on, Alan. We need to continue to pay close attention to every study that comes out and take each one on its merits or lack thereof.
Excellent analysis, Dr. Racaniello. Thank you so much for staying on top of this subject and for podcasting about XMRV. You are the voice of reason in a pretty chaotic wilderness.
Can someone please tell me why they wouldn't first check the semen of XMRV positive men for XMRV first?
There are no proven XMRV +ive patients , so you have no gold standard for this kind of study. The paper set out to look for XMRV in seminal plasma (not semen. Plasma) and they didn't find it. That was what the study was designed to do, and it did it. If the paper title said semen, your criticisms would be valid. However, they aren't…
It would indeed be wonderful to have Judy Mikovits on yr podcast. Can that be done? She is wonderful speaker.
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