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MuLv's Needs Adeno Virus to Make a Person Sick?

Discussion in 'XMRV Research and Replication Studies' started by Mya Symons, May 25, 2011.

  1. Mya Symons

    Mya Symons Mya Symons

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    I was watching the video of the CFSAC speakers and noticed that one speaker mentioned an outbreak of Adeno virus that triggered her illness. This was the same trigger for my son. I know this because a couple weeks after he started having seizures he came down with a high fever. At that point, the doctors at Children's Hospital in Seattle checked him for viruses and found an Adeno Virus. I was wondering if there could be a connection between an Adeno Virus and a Retrovirus infection that is causing CFS/ME. I found the following abstract of a medical journal article. It seems they were trying to use the two viruses together for gene therapy since alone they weren't doing the job. COULD IT BE POSSIBLE THAT A PERSON COULD CARRY SOMETHING LIKE XMRV FOR YEARS AND NOT GET SICK UNTIL IT IS TRIGGERED BY AN ADENO VIRUS (a DNA virus)--WHICH THEN ALLOWS IT TO ENTER THE CELLS AND REPRODUCE?

    After you read this, can you bump the jokes back up? We need jokes.

    Gene Ther. 1998 Sep;5(9):1251-8.

    Construction of new retroviral producer cells from adenoviral and retroviral vectors.

    Lin X.


    Source

    Protein Studies Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.


    Abstract

    A combination of adenoviral and retroviral vectors was used to construct second generation packaging cells that deliver marker genes to target cells. A vector based upon Moloney murine leukemia virus (MoMLV) was used to deliver marker genes, and an adenovirus-based delivery system was used to deliver MoMLV structural genes (gag pol and env) to cultured cells. The procedure transformed the cells into new retroviral producer cells, which generate replication-incompetent retroviral particles in the culture supernatant for transferring marker genes to target cells. The titer of the retroviral-containing supernatant generated from the second generation producer cells reached above 10(5) c.f.u./ml, which is comparable to the MoMLV-based producer cell lines currently used in human gene therapy trials. These observations suggest that this new gene transfer scheme is technically feasible. The vector and procedures may be adapted for experimental human gene therapy in which the new producer cells are transplanted into patients for continuous gene transfer.


    PMID: 9930327 [PubMed - indexed for MEDLINE] Free Article



    HERE'S ANOTHER STUDY WHERE THEY TALK ABOUT A REPLICATION-COMPETENT HYBRID OF THE ADENO VIRUS AND AN MuLv:


    Mol Ther. 2011 Jan;19(1):76-82. Epub 2010 Aug 31.

    Adenovirus-retrovirus hybrid vectors achieve highly enhanced tumor transduction and antitumor efficacy in vivo.

    Kubo S, Haga K, Tamamoto A, Palmer DJ, Ng P, Okamura H, Kasahara N.


    Source

    Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. s-kubo@hyo-med.ac.jp


    Abstract

    Murine leukemia virus (MLV)-based replication-competent retrovirus (RCR) vectors have been shown to mediate efficient, selective, and persistent tumor transduction, thereby achieving significant therapeutic benefit in a wide variety of cancer models. To further augment the efficiency of this strategy, we have developed a delivery method employing a gutted adenovirus encoding an RCR vector (AdRCR); thus, tumor cells transduced with the adenoviral vector transiently become RCR vector producer cells in situ. As expected, high-titer AdRCR achieved significantly higher initial transduction levels in human cancer cells both in vitro and in vivo, as compared to the original RCR vector itself. Notably, even at equivalent initial transduction levels, more secondary RCR progeny were produced from AdRCR-transduced cells as compared to RCR-transduced cells, resulting in further acceleration of subsequent RCR replication kinetics. In pre-established tumor models in vivo, prodrug activator gene therapy with high-titer AdRCR could achieve enhanced efficacy compared to RCR alone, in a dose-dependent manner. Thus, AdRCR hybrid vectors offer the advantages of high production titers characteristic of adenovirus and secondary production of RCR in situ, which not only accelerates subsequent vector spread and progressive tumor transduction, but can also significantly enhance the therapeutic efficacy of RCR-mediated prodrug activator gene therapy.


    PMID: 20808291 [PubMed - indexed for MEDLINE] PMCID: PMC3017434 [Available on 2012/1/4]
  2. alex3619

    alex3619 Senior Member

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    Hi Mya, this is interesting and raises some issues, but this research is about something a little different. Each virus is effective at binding to cells with certain cell markers. By combining a virus that can infect one type of cell, with the mechanisms of another virus, you can infect cells that could not otherwise be infected. This can, however, happen naturally. I do not think that at this time we can cay it is a major risk factor, however it could happen in some people and would lead to viral reservoirs that are not the traditional viral reservoirs.

    Put another way, if you have XMRV and have a severe viral infection of another kind, XMRV might suddenly find itself inside cells it could not normally infect. This is a low probability event, but the risk goes up as viral load increases.

    Personally I think the little evidence shows XMRV might lurk until you get very sick, then multiplies like crazy. The immune system sees it, fights it, but never stops fighting it because it can't eradicate XMRV, a retrovirus. This is the two hit hypothesis, but not a lot different from what you have proposed.

    However, it is clear that some viral infections would be more XMRV promoting than others under this model. It might be that adeno viruses are another class of virus that can do this, we just don't know.

    Bye
    Alex
  3. lansbergen

    lansbergen Senior Member

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    There are many adenovirus types and viruscirculating is not uncommon.

    The change that no adenovirus is circulating at the time one gets infected with a gamma retrovirus is not high.

    Reactivating of persistent adenovirus infection if one gets infectied by a gammaretrovirus would not be strange.

    http://en.wikipedia.org/wiki/Adenovirus_infection

    Although epidemiologic characteristics of the adenoviruses vary by type, all are transmitted by direct contact, fecal-oral transmission, and occasionally waterborne transmission. Some types are capable of establishing persistent asymptomatic infections in tonsils, adenoids, and intestines of infected hosts, and shedding can occur for months or years. Some adenoviruses (e.g., serotypes 1, 2, 5, and 6) have been shown to be endemic in parts of the world where they have been studied, and infection is usually acquired during childhood. Other types cause sporadic infection and occasional outbreaks; for example, epidemic keratoconjunctivitis is associated with adenovirus serotypes 8, 19, and 37. Epidemics of febrile disease with conjunctivitis are associated with waterborne transmission of some adenovirus types, often centering around inadequately chlorinated swimming pools and small lakes. ARD is most often associated with adenovirus types 4 and 7 in the United States. Enteric adenoviruses 40 and 41 cause gastroenteritis, usually in children. For some adenovirus serotypes, the clinical spectrum of disease associated with infection varies depending on the site of infection; for example, infection with adenovirus 7 acquired by inhalation is associated with severe lower respiratory tract disease, whereas oral transmission of the virus typically causes no or mild disease. Outbreaks of adenovirus-associated respiratory disease have been more common in the late winter, spring, and early summer; however, adenovirus infections can occur throughout the year.[3]

    "Ad14 (for adenovirus serotype 14), has caused at least 140 illnesses in New York, Oregon, Texas and Washington, according to a report from the Centers for Disease Control and Prevention. The illness made headlines in Texas in September, when a so-called "boot camp flu" sickened hundreds at Lackland Air Force Base in San Antonio. A 19-year-old trainee died."[4]
  4. Mya Symons

    Mya Symons Mya Symons

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    Interesting. I wonder if this Ad14 is the adenovirus that went through my son's school? For some reason a few kids who were in the wrestling program with my son got the adenovirus, but others did not. Maybe they picked it up from the mats. I still wonder why he got the seizures before the fever or other symptoms. It sounds like this Ad14 would be serious enough to trigger another virus or even an autoimmune disease. My son was sick for a little over two years after this adenovirus infection with bouts of fatigue and FMS pain (especially for a month or more after catching a cold or flu). I think it has been almost two years now since the FMS symptoms and fatigue completely dissappeared. Of course, I can't remember exactly when it was.
  5. kday

    kday Senior Member

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    Doesn't seem to make sense in my case, unless adenovirus can be spread by a tick?
  6. Daffodil

    Daffodil Senior Member

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    maybe any major assault to the immune system can trigger XMRV to reproduce a lot, be it EBV, adenovirus, Q fever, etc etc?
  7. lansbergen

    lansbergen Senior Member

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    Any stressor can activate it. How much virions will be produced and budded depends on many factors.

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