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HERVs and XMRV

Discussion in 'XMRV Testing, Treatment and Transmission' started by fairlight, Feb 8, 2010.

  1. fairlight

    fairlight

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    Why no mention of retrovirus HERV?

    Has WPI mentioned this retrovirus or done any studies?

    J Clin Virol. 2009 Sep;46(1):47-8. Epub 2009 Jun 7.

    HHV-6A infection induces expression of HERV-K18-encoded superantigen.
    Tai AK, Luka J, Ablashi D, Huber BT.

    Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, United States.

    BACKGROUND: The human endogenous retrovirus K-18 (HERV-K18) encodes a superantigen that causes deregulation of the immune system. This provirus is transcriptionally silent, but can be induced by Epstein-Barr virus (EBV) infection and IFN-alpha treatment.

    OBJECTIVES: Since the herpesvirus EBV induces HERV-K18 expression in human B cells, it was of interest to determine if other herpesviruses would have similar HERV-K18 transactivation properties. Human herpesvirus (HHV)-6A, a neurotropic virus associated with multiple sclerosis, was a logical candidate for these studies.

    STUDY DESIGN: HSB2 cells (HHV-6-negative control), HSB2-ML cells (containing latent HHV-6A genome) and HSB2/HHV-6A cells (HSB-2 cells productively infected with HHV-6A) were compared for their level of HERV-K18 transcription, using quantitative RT-PCR. RESULTS: Latently infected HSB2-ML cells showed a significant increase in HERV-K18 RNA compared to the control cells. HERV-K18 expression was even greater in HSB2 cells productively infected with HHV-6A for 78h.

    CONCLUSION: These results imply that HHV-6A, either in latent form or during acute infection, directly transactivates HERV-K18. This HERV-K18 induction may be mediated through IFN-alpha that is produced by the HHV-6A-infected cells. The functional implications of superantigen expression are discussed.

    http://www.ncbi.nlm.nih.gov/sites/entrez/19505843
  2. usedtobeperkytina

    usedtobeperkytina Senior Member

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    Clay, Alabama
    Is this the Defrietas virus?

    Tina
  3. fairlight

    fairlight

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    http://www.jimmunol.org/cgi/content/full/177/4/2056



    EBV, a ubiquitous human herpesvirus, is the causative agent of infectious mononucleosis and is associated with many carcinomas. We have previously shown that the EBV latent genes LMP-1 and LMP-2A (for latent membrane proteins 1 and 2A), transactivate a human endogenous retrovirus (HERV), HERV-K18, in infected B lymphocytes. The envelope (Env) protein of HERV-K18 encodes a superantigen that strongly stimulates a large number of T cells. In this study we report that HERV-K18 env is transactivated even earlier in the infection process, before the establishment of latency; namely, we found that EBV, through its interaction with its cellular receptor CD21, induces the HERV-K18 env gene in resting B lymphocytes. This transactivation is direct and immediate, as up-regulation of transcripts can be detected within 30 min after EBV exposure. Thus, EBV binding to human CD21 on resting B cells triggers the expression of an endogenous superantigen. The biological significance of this superantigen expression for the EBV life cycle is discussed
    -------------------------------------------------------------
    -Is a Retrovirus in Our DNA Responsible for Chronic Fatigue Syndrome & Multiple Sclerosis?
    Tuesday June 24, 2008

    New research points to an ancient retrovirus as a possible partial cause of chronic fatigue syndrome (CFS or ME/CFS) and multiple sclerosis (MS).

    This retrovirus is called HERV-K18, and it's part of the human genetic makeup. Researchers say it activates when you have a "smoldering infection" of the Epstein-Barr virus (EBV) and HHV-6 (which both have long been believed to have an important connection to ME/CFS.)

    The study uncovered that people whose ME/CFS or MS was triggered by infection mononucleosis (EBV) were at higher risk for HERV-K18 activation. That activation starts a chain reaction that leads to a strong T-cell response that's believed to deplete your immune system over time. Researchers say HHV-6 can activate HERV-K18 as well, as can immune activation.

    It's not surprising that science is discovering links between ME/CFS and MS.

    More than 75% of MS patients meet the criteria for ME/CFS.
    Fatigue is often the most disabling symptom of ME.
    The conditions share characteristics including:
    Gray matter atrophy
    Impaired cerebral glucose metabolism
    Autonomic nervous system activity
    Altered patterns of brain activity
    The study suggests that this retrovirus could be behind some of the shared symptoms of the two conditions. The lead researcher - Brigitte Huber, PhD of the Tufts University School of Medicine - now has a National Institutes of Health grant to study this further.

    To me, this is an exciting study because it helps explain why a common virus, that has very little effect on most people can have such a severe impact on others. It's also seems like something that could lead to better diagnostic tests and treatments. I'm keeping my fingers crossed for this one.

    http://chronicfatigue.about.com/b/2...ronic-fatigue-syndrome-multiple-sclerosis.htm
  4. fairlight

    fairlight

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    Tina-good question...

    maybe someone else knows?
  5. cfs since 1998

    cfs since 1998 *****

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    I don't know, but Mike Holmes apparently had scanning electron micrographs of infectious retroviruses budding from cells, and DeFreitas found her virus in close contacts of CFS patients that were healthy but not in unexposed controls. It seems the virus they were looking at wasn't ERV, but there's always a possibility, since no one seems to know just what it was they were looking at. Also if it was this ERV I am not sure if they would have found antibodies to a certain sequence of HTLV?

    Anyone know if any CFS patients have taken alpha interferon and how they reacted?
  6. gracenote

    gracenote All shall be well . . .

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    I was on peginterferon alfa-2b by injection for 7 to 8 months. It was for treatment of an acute infection of Hepatitis C. It made me very ill and I quit a month early as it felt so very very toxic and damaging. Fortunately, I cleared the Hep C. It took me months to recover from the debilitating effects of treatment. I even have some PTSD type symptoms from being on it. After I started recovering from the effects of the drug, I improved in my health a little bit over the next year. I've since gone downhill.

    My doctor mentioned that I could keep taking interferon in a lower dose but I wouldn't even consider it at the time. I think there might be something positive to continuing. But yikes!
  7. Hope123

    Hope123 Senior Member

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    Human Endogenous Retroviruses Demystified

    This is a general article about HERVs that is quite technical in parts. I have not read it yet. I am posting since people seem to have questions about HERVs.

    Attached Files:

  8. Abraxas

    Abraxas Senior Member

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    Thanks Hope, It'll make an intersting read when I get round to it :Retro smile:
  9. Hope123

    Hope123 Senior Member

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    I'm gradually beginning to read a bit about HERVs, especially as Kurt has pointed out multiple times that what the WPI has been detecting might be HERVS. Here are my thoughts:

    1. If we're looking at a HERV, why was the WPI able to get positive culture results? Most HERVs as I understand do not manufacture active retroviral particles that can infect other cells. HERV-Ks can manufacture particles (?budding seen on EM photographs from WPI?) but these are not infectious. I've also read briefly that there are techniques available to identify if particles are HERV-K so this is a possibliity for the WPI to explore.

    2. The HERVs that interact with MLV antibodies are HERV-H, HERV-I, and HERV-R families but these don't produce particles.

    3. There still is the possibility that we're dealing with an entirely new HERV.

    4. It would have been interesting if the WPI had done more co-culture/ EM studies with the control group. Small numbers of these were done.
  10. kurt

    kurt Senior Member

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    USA.Earth
    Good points.

    If you have not already read this, I suggest reading the

    Rumor Viruses article/chapter.

    The idea that WPI may be finding HERVs mostly applies to the antibody testing (serology and culture use antibodies). I did read somewhere that there are HERV K family viruses that produce reverse transcriptase, which is found in CFS, so that is interesting. And also there was one pub somewhere that found a HERV K reacting with MuLV antibodies, although most of the MuLV types are HERV type II.

    As for amplification, that is possible with a HERV if a protein used in the culture assay happens to trigger HERV activation in the cell line's DNA. And WPI did use a prostate cancer cell line, which is interesting.

    I agree, we might be dealing with a new HERV, although WPI did say they blasted the suspected XMRV antigen against human DNA and got no hit so that might rule out a HERV. However, the lab they used (Silverman's) had been studying that exact same antigen so that also does not rule out contamination.

    Another possibility is that WPI PCR positives were false positives produced by HERVs interacting with reagents, but not actual sequence hits on HERVs. The numbers make sense if this happened because there is more HERV activity in PWC than in controls.

    Also, WPI may have found a novel MuLV type retrovirus with their serology testing. So the different tests might have different reasons for being positive.

    These alternate explanations would seem to be out on a limb, until you go through the history of retroviral hunting in the Rumor Viruses chapter (linked above). This has happened again and again with other diseases.

    The EM study really says nothing to me, because HERV particles can be the size of gamma retroviruses.
  11. Hope123

    Hope123 Senior Member

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    That was a good article Kurt...........technical and still plowing through parts of it but it makes good reading alongside the Science and other XMRV articles.

    To me, this is actually a fairly optimistic article because it talks about all the different techniques to look for retroviruses and I can see multiple ideas here which could be employed for potential CFS retroviral involvement, whether XMRV specifically pans out or not. One method I'd like WPI to look at is antibody labelling of the particles they are seeing on EM to see if these are known HERV particles vs. something else. Another would be looking at the insertion sites to distinguish retroviruses vs. HERVs. Lots of interesting ideas here.

    Another interesting point was the part about MS and HERVs where detection of a specific HERV was correlated with disability progression in MS. Makes one wonder if XMRV/HERV detection is correlated with severity? duration? of CFS. We have little data on this and WPI's characterization of their CFS subjects I am still unclear on. (In one talk, I heard they were fairly severe; in another, that it varied among the group.)
  12. mezombie

    mezombie Senior Member

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    Thanks for asking the right questions

    It's articles like this, Kurt, that make me miss my former reading and information processing skills!:sad:

    I'm posting the conclusion because I feel this deserves a bit more exposure on this forum:

  13. CBS

    CBS Senior Member

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    Kurt,

    Thanks for the good read! I'm diving in tonight (and tomorrow).

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