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HHV-6 Hidden in Chromosomes Can Be Passed from Parents to Children

Discussion in 'Other Health News and Research' started by Kati, Mar 9, 2010.

  1. Kati

    Kati Patient in training

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    http://www.sciencedaily.com/releases/2010/03/100308151055.htm



  2. _Kim_

    _Kim_ Guest

    Great score Kati! This may be the biggest news since XMRV hit the newstands.

    Check out the cast of characters that co-authored this baby:

    The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro

    Jesse H. Arbuckle, Maria M. Medveczky, Janos Luka, Stephen H. Hadley, Andrea Luegmayr, Dharam Ablashi, Troy C. Lund, Jakub Tolar, Kenny De Meirleir, Jose G. Montoya, Anthony L. Komaroff, Peter F. Ambros, and Peter G. Medveczky

    Abstract
    Previous research has suggested that human herpesvirus-6 (HHV-6) may integrate into host cell chromosomes and be vertically transmitted in the germ line, but the evidence—primarily fluorescence in situ hybridization (FISH)—is indirect.We sought, first, to definitively test these two hypotheses. Peripheral blood mononuclear cells (PBMCs) were isolated from families in which several members, including at least one parent and child, had unusually high copy numbers of HHV-6 DNA per milliliter of blood. FISH confirmed that HHV-6 DNA colocalized with telomeric regions of one allele on chromosomes 17p13.3, 18q23, and 22q13.3, and that the integration site was identical among members of the same family. Integration of the HHV-6 genome into TTAGGG telomere repeats was confirmed by additional methods and sequencing of the integration site. Partial sequencing of the viral genome identified the same integrated HHV-6A strain within members of families, confirming vertical transmission of the viral genome. We next asked whether HHV-6A infection of nave cell lines could lead to integration. Following infection of nave Jjhan and HEK-293 cell lines by HHV-6, the virus integrated into telomeres. Reactivation of integrated HHV-6A virus from individuals’ PBMCs as well as cell lines was successfully accomplished by compounds known to induce latent herpesvirus replication. Finally, no circular episomal forms were detected even by PCR. Taken together, the data suggest that HHV-6 is unique among human herpesviruses: it specifically and efficiently integrates into telomeres of chromosomes during latency rather than forming episomes, and the integrated viral genome is capable of producing virions.

    p.s. I have the full text version and tried to post it in the Library, but the pdf is too large to upload as one attachment, so it's in two parts
  3. flybro

    flybro Senior Member

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    pluto
    Good find Kati

    Thanks
  4. Kati

    Kati Patient in training

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    It is an exciting discovery- and probably very meaningful for ME/CFS. Looking forward to hear the scientists' comments-
  5. _Kim_

    _Kim_ Guest

    Kati, is it okay if we change the title to 'HHV-6A' instead of 'infectious virus'?
  6. Kati

    Kati Patient in training

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    Go right ahead Kim, it will be easier to track the article- I just copied and pasted the title of the article in the journal
  7. _Kim_

    _Kim_ Guest

    um, we'll need someone who actually has permissions to do that to make the change.
  8. Kati

    Kati Patient in training

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    I have done it actually!!!!
    You happy with the title or you got another suggestion?

    ETA- err I don't think I changed the title in the end, more like the sub-title... Will look out for a mod.
  9. _Kim_

    _Kim_ Guest

    The HHV-6 Foundation says:

    University of South Florida team publishes a landmark study in PNAS
    [​IMG]
    Left to right: Peter Medveczky, Jesse Arbuckle, Maria Medveczky, Shara Pantry
    Photo University of South Florida


  10. _Kim_

    _Kim_ Guest

    Questions Raised by These Studies.
  11. Mark

    Mark Acting CEO

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    Science Daily wonders:
    "Since the telomeres are important in cellular aging and in cancer, could the insertion of viral DNA in the telomeres have any effect on a cell's tendency to age or to turn cancerous?"

    Can I ask the scientists on here: is it conceivable that the viral DNA could insert itself into the telomeres in such a way that rather than making a cell age more quickly, the insertion could somehow acts as a stopper to the gradual attrition of telomeres? In other words, cells with viral DNA inserted might survive longer because once the telomeres are worn down to the point where the viral DNA is, that bit effectively protects itself from getting deleted? I'm sure it doesn't work quite like that, but that's why I'm asking...

    Because if the telomere insertion could work in that way, it might be time to look up that old thread called something like "Does anyone else look young for their age?"...
  12. natasa778

    natasa778 Senior Member

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    This is actually not news as was 'discovered' few years ago by a Japanese team and then confirmed by a British-led team... this says a lot about media reporting... Not my intention to spoil the joy as it is really great and I'm looking forward to more about this. Great that this type of research is happening and also great that it is finally getting reported!!
  13. Athene

    Athene Never give up

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    Is this integration with the chromosomes the same thing that XMRV does?
    Is anyone clever enough to understand if this has implications for XMRV research in terms of transmission etc?
  14. bullybeef

    bullybeef Senior Member

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    This is really freaky. Both my young sons have had these forms of rashes, my youngest only last week, and I had a widespread rash about a year before I left work (2004). I forgot what my GP said it was, but upon looking at some pictures, I found it. And low and behold it was infectious mononucleosis: http://en.wikipedia.org/wiki/File:Cross_Reaction_Rash.JPG

    I can't believe how many links I am finding. I also had some blood tests done recently, and the practice nurse didn't do a infectious mononucleosis test (I'd like to think she either didnt know I once had it, or simply forgot).

    It is really interesting to discover exactly what could have activated my illness.
  15. Dr. Yes

    Dr. Yes Shame on You

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    That previous research was on what was called Chromosomally Integrated HHV-6 (the name may have to be modified now!) or CIHHV-6, which referred to a relatively rare condition that indeed has been known about for a few years...from the HHV-6 Foundation website:

    "In rare cases, HHV-6 i found to be integrated into human chromosomes in high copy numbers producing unusually high viral loads in the whole blood and serum. Both HHV-6A and B have been found integrated into the chromosomes of immunocompetent patients at persistently high levels of viral DNA in blood, sera, and hair follicles (Ward 2006). A large study in Japan showed that the incidence is 0.2% but two smaller studies from the UK suggest it may be approximately 0.8 and 1.5%. Children hospitalized for seizures or encephalitis have higher rates of CIHHV-6, reported to be 2.9-3.3% (Leong 2007)."

    But the very surprising new (though preliminary) finding in this study is that HHV-6 does not appear to use the normal form of latency for herpesviruses at all, but instead always integrates into host chromosomes. As their abstract concludes:

    Other herpesviruses go into latency in our cells by hiding small circular packets of DNA in our nuclei. Apparently this was assumed to be true of HHV-6 (and I find it surprising that no one bothered to look??), but it turns out - from this one study at least - that there is no evidence of episome formation in HHV-6 infected PBMC's or deliberately infected experimental cell lines.... Instead, in both cases the virus integrated itself into the telomeres of certain chromosomes, and could be re-activated chemically:

    Anyway, since those chemicals could induce chromosomally-stored HHV-6 (both from newly infected cell lines and from the blood cells of CIHHV-6 patients) out of latency and to produce virions, this is probably not a "benign" storage of HHV-6 in chromosomes in either case. (Previously there was debate about whether CIHHV-6 could replicate at all.)

    (from natasa778):
    Yes! Dr. Ablashi has been complaining for years about the lack of interest in and poor funding of HHV-6 research by the NIH (for whom he worked), etc; remember his testimony at the November CFSAC meeting? Hopefully now things will start to change.

    (from Athene):
    XMRV integrates into the genome itself, while HHV-6 only does so in the telomeres (bits of non-coding DNA at the ends of the chromosome). The telomeres have no genes, and so are mostly ignored until a cell divides, when most (but not all) of the telomere is copied along with the rest of the chromosome.

    I don't see how this particular finding would relate to XMRV research, unless one speculation that has been thrown out there - that a retrovirus can somehow get integrated into the genome of HHV-6 - turns out to be true. However, that is a pure speculation by one guy (I think a pharmaceutical company scientist), as far as I know. Of course, I'm not what one would normally call 'clever'! :confused: <---(me)

    From bullybeef:
    The rash depicted there is a cross-reaction rash that people with EBV infectious mononucleosis develop when taking most types of antibiotics at the same time. That particular rash isn't caused by the virus alone, and I don't know if such cross-reactions take place with HHV-6 or CMV and antibiotics. Were you and your sons all on antibiotics when you developed these rashes?

    Infectious mononucleosis (which technically is EBV, though CMV can cause something very similar) itself can cause a rash, though I don't know how it presents (you've probably found out by now!). HHV-6 variant B is well known to cause a particular kind of rash called roseola in children age 2 years or younger. But to my knowledge only immunocompromised adults can get a rash from HHV-6.
  16. bullybeef

    bullybeef Senior Member

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    Thanks Doc for the info, it's beginning to make perfect sense. Let me elaborate:

    My eldest son had, what our GP suggested, a very rare rash condition. I have been racking my brain to recall it and I've just found it on the net. It was Henoch–Schnlein purpura. It was only the 2nd time my GP had ever treated it. But we did have a particular issue. My son only has one kidney, and HSP can have a negitive effect on the kidneys. So he was in hospital for a week, whilst the doctors tried to work out what was wrong with him, and how to treat him. He also had baby arthritis. So, although my memory is vague, he was on antibiotics because of this (I think it was intravenous). If you look at HSP on Wikipedia, right at the bottom it gives William Osler a mention. Scary or what?!!

    When I had mononucleosis, again it is very vague, but I think I was also on antibiotics. Has this info been passed onto my ME consultant? Did this lead to my diagnosis? I have no idea.

    My youngest son has just got over herpes simplex virus, but there is another rash occurring. That is why I have been looking into it. The scary thing is, this new rash does look like HSP!!
  17. natasa778

    natasa778 Senior Member

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    The prevalence of chromosomally integrated human herpesvirus 6 genomes in the blood of UK blood donors.

    A lesser-recognized form of human herpesvirus 6 (HHV-6) persistence is integration of the viral genome in a host chromosome and high viral copy numbers in blood or sera are characteristic of this phenomenon. A cross-sectional study was performed to determine the frequency of high HHV-6 viral loads in whole blood (>6 log(10) copies/ml) in a population of blood donors in London, UK. Blood samples from 500 anonymized blood donors were collected from one donation center, DNA extracted, and quantitative realtime PCR used to measure viral load. Four samples (0.8%) were found to have high viral copy numbers of HHV-6 (median 6.7 log(10) copies/ml; range 6.5- 6.9 log(10) copies/ml). Cellular DNA was also quantitated using qRT-PCR for beta-globin. By comparing these two results, we calculated that there were between two and five copies of HHV-6 present per cell in these four donors. The median viral load detected in plasma from the four individuals was 3.8 log(10) copies/ml (range 3.5-4.0 log(10) copies/ml). All samples were HHV-6 variant B. In addition, a retrospective analysis of all diagnostic blood samples performed for HHV-6 in our center showed a prevalence of 2.9% of high viral loads characteristic of integration. In conclusion, high viral copy numbers of HHV-6, representing a population of viral integration, is detected in 0.8% of UK blood donors. The presence of high HHV-6 viral loads in healthy normal individuals reiterates the need to consider the confounding effect of HHV-6 viral integration in any laboratory diagnosis of HHV-6 infection.
    Leong HN, et al Division of Infection and Immunity, Centre for Virology, Hampstead Campus, Royal Free and University College Medical School, London, UK. J Med Virol. 2007 Jan;79(1):45-51.
  18. Dr. Yes

    Dr. Yes Shame on You

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    Btw bullybeef I edited that part of my post while you were posting: I did remember that EBV can cause a rash by its lonesome, and double-checked on a couple medical sites... it's usually not an itchy rash like the antibiotic-reactive one, though.

    Oh, and in case it hasn't been ordered by your son's doctor yet, it's a good idea to do urinalysis in HSP cases, looking for blood or protein in the urine, as kidney damage/ disease is sometimes caused by it. Though that happens more often in adults than in kids. Just something you might want to keep your eyes on.
  19. bullybeef

    bullybeef Senior Member

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    Sorry, I understand you now. No, I don't think any of us were on antibiotics prior to the rashes. And you are correct, I don't recall the mono I had being persistently itchy. What was weird was the speed it cleared up. It started as a blemish on my chest, and after week, my whole torso and thighs were covered, yet it was gone in a couple of days.

    Oh, and my eldest was in hospital on two separate occasions for his arthritis and HSP.
  20. JillBohr

    JillBohr Senior Member

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    Thank you Kati! I have been following the HHV6 Foundation off and on the last year. My oldest son has autism and seizure disorder. According to their website, lamotrigine, is effective against HHV6-B but not HHV6-A. My son takes it (aka lamictal) for his seizures. http://www.hhv-6foundation.org/treatment.htm

    Oh, btw, my kids also come down with the strangest skin rashes. My youngest son was diagnosed with Pityriasis rosea just last December. It still hasn't cleared up all the way and it is now March.

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