Bob
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There have been a couple of studies (one paper & one abstract) recently published by William Switzer of the CDC, which have a significant impact on the XMRV contamination debate.
These studies have been discussed on the forum before, but I think that the discussions may have been buried in long threads, so I thought it might be helpful to repost the information here.
Here are details of the two studies...
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No Association of Xenotropic Murine Leukemia Virus-Related Viruses with Prostate Cancer
William M. Switzer, Hongwei Jia, HaoQiang Zheng, Shaohua Tang, Walid Heneine
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0019065#abstract0
Although Switzer concluded that there is no association between XMRV and prostate cancer, based on the findings of this study, he did detect XMRV in the tissue of 3 prostate cancer samples, but he could not detect XMRV in the blood of those XMRV-positive patients. He concluded that further investigation of XMRV is needed.
"Sequence analysis of the PCR-positive specimens was highly informative because it confirmed that all three specimens were XMRV-related. Also, the finding of a viral strain in three prostate cancer patients that is distinct from the XMRV seen in previous studies is significant and demonstrates a broader viral diversity. This would be an expected result consistent with virus evolution during spread and persistence."
The significance of Switzer's study is...
1. Switzer confirms that XMRV is a real wild human virus.
2. Switzer concludes that the genetic variation is consistent with normal human infection.
3. Switzer admits that he cannot detect XMRV in the blood of XMRV-positive prostate cancer patients, using established methodologies. This has relevance for all of the other negative XMRV studies.
4. Switzer confirms that his findings not due to contamination.
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The following two abstracts look like they are based on the same study...
Extensive Genetic Recombination in the XMRV Genome
William Switzer, W Heneine1, M Prosperi, and M Salemi
Presented at the 18th Conference on Retroviruses and Opportunistic Infections (CROI) 2011
http://retroconference.org/AbstractSearch/Default.aspx?Conf=20&Abs=40126
Murine leukemia viruses (MuLV) and Xenotropic MuLV-related viruses exhibit inter-tropic complex recombination patterns
Mattia C F Prosperi , William M Switzer, Walid Heneine and Marco Salemi
6 June 2011
Presented at the '15th International Conference on Human Retroviruses: HTLV and Related Viruses'
http://www.retrovirology.com/content/8/S1/A235
Conclusion:
"Given the evidence of inter-tropic recombination in MuLV, detection and classification of recombination in XMRV using different MuLV tropism prototypes should be interpreted with caution ... These results suggest that identification of parental strains of the potential recombinants is difficult and that recombination in the highly genetically related MuLV have been occurring for some time."
The Paprotka et al. paper (i.e. Paprotka, Coffin and Pathak) ruled out everything for XMRV other than a recombination event happening in the specific cell line that they studied. This CDC/Switzer study points out that, contrary to John Coffin's conclusions in the Paprotka et al. study, there are a myriad of ways that XMRV could potentially have been created by a recombination event, and that the prostate cancer cell line might just be one example of many possible recombination events. Switzer draws very different conclusions to Paprotka et al., and directly challenges their study's conclusion of a 'one in a trillion' chance of a recombination event.
The significance of this paper is that Switzer directly challenges, Coffin's theories about the recombination history of XMRV. Switzer appears to be saying that Coffin's 'one in a trillion' conclusion is mistaken, and that there is a vast potential for possible recombination events to have happened to create XMRV.
This study hasn't been published yet, so it is premature to make any definite conclusions from it, but taken together with the published Switzer study, above, the two studies challenge most aspects of the Paprotka et al. (e.g. Paprotka, Coffin and Pathak) recombination study.
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Switzer's sequences published in genbank:
Division of HIV/AIDS Prevention, Ceners for Disease Control and Prevention.
Switzer,W.M., Jia,H., Zheng,H., Tang,S. and Heneine,W.
10th May 2011
Xenotropic MuLV-related virus isolate 5935 polymerase (pol) gene, partial cds
http://www.ncbi.nlm.nih.gov/nuccore/HQ116790.1
Xenotropic MuLV-related virus isolate 5956 gag protein (gag) gene, partial cds
http://www.ncbi.nlm.nih.gov/nuccore/HM003612.1
Xenotropic MuLV-related virus isolate 6203 envelope (env) gene, partial cds
http://www.ncbi.nlm.nih.gov/nuccore/HM003611.1
Xenotropic MuLV-related virus isolate 5956 envelope (env) gene, partial cds
http://www.ncbi.nlm.nih.gov/nuccore/HM003610.1
Xenotropic MuLV-related virus isolate 6203 polymerase (pol) gene, partial cds
http://www.ncbi.nlm.nih.gov/nuccore/HM003609.1
Xenotropic MuLV-related virus isolate 5956 polymerase (pol) gene, partial cds
http://www.ncbi.nlm.nih.gov/nuccore/HM003608.1
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John Coffin's recombination paper:
Recombinant Origin of the Retrovirus XMRV
Tobias Paprotka, Krista A. Delviks-Frankenberry, Oya Cingz, Anthony Martinez, Hsing-Jien Kung, Clifford G. Tepper, Wei-Shau Hu, Matthew J. Fivash Jr., John M. Coffin, Vinay K. Pathak
31 May 2011
Sciencexpress
http://www.sciencemag.org/content/early/2011/05/31/science.1205292.full.pdf
---
These studies have been discussed on the forum before, but I think that the discussions may have been buried in long threads, so I thought it might be helpful to repost the information here.
Here are details of the two studies...
---
No Association of Xenotropic Murine Leukemia Virus-Related Viruses with Prostate Cancer
William M. Switzer, Hongwei Jia, HaoQiang Zheng, Shaohua Tang, Walid Heneine
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0019065#abstract0
Although Switzer concluded that there is no association between XMRV and prostate cancer, based on the findings of this study, he did detect XMRV in the tissue of 3 prostate cancer samples, but he could not detect XMRV in the blood of those XMRV-positive patients. He concluded that further investigation of XMRV is needed.
"Sequence analysis of the PCR-positive specimens was highly informative because it confirmed that all three specimens were XMRV-related. Also, the finding of a viral strain in three prostate cancer patients that is distinct from the XMRV seen in previous studies is significant and demonstrates a broader viral diversity. This would be an expected result consistent with virus evolution during spread and persistence."
The significance of Switzer's study is...
1. Switzer confirms that XMRV is a real wild human virus.
2. Switzer concludes that the genetic variation is consistent with normal human infection.
3. Switzer admits that he cannot detect XMRV in the blood of XMRV-positive prostate cancer patients, using established methodologies. This has relevance for all of the other negative XMRV studies.
4. Switzer confirms that his findings not due to contamination.
---
The following two abstracts look like they are based on the same study...
Extensive Genetic Recombination in the XMRV Genome
William Switzer, W Heneine1, M Prosperi, and M Salemi
Presented at the 18th Conference on Retroviruses and Opportunistic Infections (CROI) 2011
http://retroconference.org/AbstractSearch/Default.aspx?Conf=20&Abs=40126
Murine leukemia viruses (MuLV) and Xenotropic MuLV-related viruses exhibit inter-tropic complex recombination patterns
Mattia C F Prosperi , William M Switzer, Walid Heneine and Marco Salemi
6 June 2011
Presented at the '15th International Conference on Human Retroviruses: HTLV and Related Viruses'
http://www.retrovirology.com/content/8/S1/A235
Conclusion:
"Given the evidence of inter-tropic recombination in MuLV, detection and classification of recombination in XMRV using different MuLV tropism prototypes should be interpreted with caution ... These results suggest that identification of parental strains of the potential recombinants is difficult and that recombination in the highly genetically related MuLV have been occurring for some time."
The Paprotka et al. paper (i.e. Paprotka, Coffin and Pathak) ruled out everything for XMRV other than a recombination event happening in the specific cell line that they studied. This CDC/Switzer study points out that, contrary to John Coffin's conclusions in the Paprotka et al. study, there are a myriad of ways that XMRV could potentially have been created by a recombination event, and that the prostate cancer cell line might just be one example of many possible recombination events. Switzer draws very different conclusions to Paprotka et al., and directly challenges their study's conclusion of a 'one in a trillion' chance of a recombination event.
The significance of this paper is that Switzer directly challenges, Coffin's theories about the recombination history of XMRV. Switzer appears to be saying that Coffin's 'one in a trillion' conclusion is mistaken, and that there is a vast potential for possible recombination events to have happened to create XMRV.
This study hasn't been published yet, so it is premature to make any definite conclusions from it, but taken together with the published Switzer study, above, the two studies challenge most aspects of the Paprotka et al. (e.g. Paprotka, Coffin and Pathak) recombination study.
---
Switzer's sequences published in genbank:
Division of HIV/AIDS Prevention, Ceners for Disease Control and Prevention.
Switzer,W.M., Jia,H., Zheng,H., Tang,S. and Heneine,W.
10th May 2011
Xenotropic MuLV-related virus isolate 5935 polymerase (pol) gene, partial cds
http://www.ncbi.nlm.nih.gov/nuccore/HQ116790.1
Xenotropic MuLV-related virus isolate 5956 gag protein (gag) gene, partial cds
http://www.ncbi.nlm.nih.gov/nuccore/HM003612.1
Xenotropic MuLV-related virus isolate 6203 envelope (env) gene, partial cds
http://www.ncbi.nlm.nih.gov/nuccore/HM003611.1
Xenotropic MuLV-related virus isolate 5956 envelope (env) gene, partial cds
http://www.ncbi.nlm.nih.gov/nuccore/HM003610.1
Xenotropic MuLV-related virus isolate 6203 polymerase (pol) gene, partial cds
http://www.ncbi.nlm.nih.gov/nuccore/HM003609.1
Xenotropic MuLV-related virus isolate 5956 polymerase (pol) gene, partial cds
http://www.ncbi.nlm.nih.gov/nuccore/HM003608.1
---
John Coffin's recombination paper:
Recombinant Origin of the Retrovirus XMRV
Tobias Paprotka, Krista A. Delviks-Frankenberry, Oya Cingz, Anthony Martinez, Hsing-Jien Kung, Clifford G. Tepper, Wei-Shau Hu, Matthew J. Fivash Jr., John M. Coffin, Vinay K. Pathak
31 May 2011
Sciencexpress
http://www.sciencemag.org/content/early/2011/05/31/science.1205292.full.pdf
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