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  1. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    I'm worn out here. Hope that someone else will give this a stab.
  2. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    OK, perhaps I have been working with MLVs in culture for too long, where any virus that lands in a nonpermissive site in a chromosome is quickly overrun by new viruses that remain active after integration, such that every cell is turned into a virus factory in short order. Or perhaps I am...
  3. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    Dusty Miller said: ↑ On the other hand, MLV-like viruses poorly infect nondividing cells, such as neural cells, and the data from XMRV-infected monkeys support this prediction (Onlamoon et al. Table 1, showing little if any infection of brain). More word games, what fun. So you think a dental...
  4. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    No worries, the bloggers involved and my local IRB actually did us a favor, in spite of their intentions. My lab members and I, and Ecoclimber, who was helping us with the design of the trial, didn't know at the time that Jay Levy's group was essentially doing the study we wanted to do. Their...
  5. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    Sorry for taking so long to respond to your questions. I looked over the abstract of the Holmes papers you sent me. While the approaches he took to finding viruses are a good start, they are not very sensitive (the reverse transcriptase [RT] assay) and don't tell you what virus is present...
  6. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    Bob, you are absolutely correct and are not mistaking the terminology!
  7. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    The Knox et al. paper from the Jay Levy lab (http://www.ncbi.nlm.nih.gov/pubmed/21628393) goes a long way toward showing that no MLV-like retroviruses are present in CFS patients. They used an assay that is capable of detecting many different types of MLV in an attempt to detect such viruses in...
  8. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    Dusty Miller said: ↑ Interesting questions. My understanding is that these simple retroviruses have no easy way to go latent. Unlike herpesviruses, for example, which have complex genetic machinery to regulate their active versus latent states, simple retroviruses like XMRV and MoMLV are always...
  9. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    I agree with your concern about my example of the "harmless" xenotropic ERV in NZB mice. I read over some of the early descriptions of the generation of inbred mice in New Zealand, and some of Jay Levy's publications from the 1970's on the detection of xenotropic virus in these and other strains...
  10. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    Of course I know what putative means. I like the term 'predicted' instead, but no matter. What you need to know is that molecular biologists discovered some time ago that machinery exists in every cell to convert DNA information to RNA, and then to specific proteins. The code for this...
  11. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    There clearly IS an env gene in the 22Rv1/CWR-R1 sequence posted in GenBank. A typical gene consists of a transcriptional promoter (including sequences that regulate transcription), an open reading frame downstream of the promoter that encodes a protein, and signals that terminate transcription...
  12. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    Perhaps you know, I haven't had time to look. Do the NZB mice have a functional Xpr1 receptor for xenotropic viruses, such as the NZB virus? If not, is it hypothesized that the NZB virus causes disease without being able to infect the cells of the NZB mouse?
  13. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    I can't imagine why you persist in calling the 22Rv1/CWR-R1 sequence (http://www.ncbi.nlm.nih.gov/nuccore/FN692043.2) incomplete. I just did a BLAST search on this sequence, and it matches the VP62 XMRV sequence very well, with only 5 base mismatches and two single-base gaps. We know the VP62...
  14. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    Thank you for the encouragement to continue discussions with patients here. My experience on this site is far better than I had on the http://www.mecfsforums.com/ site! The discussion here is polite and informative, while that on the mecfsforums was hostile. Before I respond to your questions...
  15. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    What is your question? This paper finds that there are two fully-infectious endogenous retroviruses in domestic cats from Japan, and that these viruses can recombine with the well-known exogenous retroviruses of cats. An interesting report that has me looking suspiciously at my two house cats...
  16. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    Good call, I stand corrected. I hadn't looked at the Onlamoon study for some time, so I read it again. It's a very dense paper, but I agree, the data indicate persistence of XMRV in rhesus macaques beyond the chronic phase of virus replication. Frankly, I can't follow all of the presentation...
  17. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    Interesting questions. My understanding is that these simple retroviruses have no easy way to go latent. Unlike herpesviruses, for example, which have complex genetic machinery to regulate their active versus latent states, simple retroviruses like XMRV and MoMLV are always 'on'. They have...
  18. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    You may have gotten your wish. When I look at the current 22Rv1/CWR-R1 sequence in GenBank, http://www.ncbi.nlm.nih.gov/nucleotide/334717372?report=genbank&log$=nucltop&blast_rank=1&RID=0V2U9EKY01S , I see the following annotation: mat_peptide 5754..7691 /product="putative envelope...
  19. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    PCR is only useful if you know what you are looking for. To perform PCR, short DNA 'primers' are made that bind to regions of the DNA of interest that are fairly close together, and thermocycling with DNA polymerase is performed to amplify this specific sequence. If you don't know the sequence...
  20. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    Nicely stated. However, I will bring up some other data that I remember from my early days in retrovirology. Not totally sure if all of it is correct. There are many murine leukemia viruses that can infect laboratory mice, unlike the xenotropic viruses that we have been discussing. They...
  21. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    Regarding the apparent lack of an env gene in the 22Rv1 virus sequence, this is simply a problem with the annotation of this sequence. That is, someone left out a description of the Env protein, even though an open reading frame from which the Env protein is translated is clearly present in the...
  22. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    "But, because human cells can be infected by a virus in animals or in cell culture doesn't imply that the virus is a human pathogen." I am simply making a logical statement here. A threat of rain doesn't imply that it will rain.
  23. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    With all due respect, the scientific community has not ignored the possibility that retroviruses like XMRV might spread in the human population, and much research has been done to detect such retroviruses in humans. When retroviruses were first found to cause cancer in animals, it was obvious to...
  24. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    A quote from the last paragraph of a paper from my lab (Knouf et al., J Virol 83:7353, 2009): "Finally, production of XMRV by 22Rv1 and potentially other prostate cancer cell lines should be carefully considered from the standpoint of possible virus transmission to laboratory personnel, to...
  25. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    When the paper came out, I was impressed, until I looked into the details.
  26. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    Thank you for being alert and asking good questions. The paper by Schlaberg et al. is fatally flawed and should not have been published. If there was a place on the PNAS website to post comments on papers, I would have done so long ago. These authors make a classic mistake of using polyclonal...
  27. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    Yes, I know this paper, but it is old news. In 1977, Suzuki et al. (Gann 68:99, 1977) reported similar findings that human cancers transplanted into mice readily acquired retroviruses (type C viruses). Here's the Abstract: "Type-C virus particles were revealed by electron microscope in 6 of 9...
  28. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    What I mean by "The original findings of XMRV association with prostate cancer and CFS have not been confirmed by others," is just that. Many carefully done studies have failed to confirm the presence of XMRV in patients with prostate cancer or CFS. For example, Aloia et al. (Cancer Research...
  29. Dusty Miller

    Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

    You are correct, this is what you posted. The section that was left out was: "It is now known that XMRV was not present in the original tumor from which 22Rv1 cells were derived, but instead, arose during passage of these cells as a xenograft in mice. The original findings of XMRV association...