The 12th Invest in ME Research Conference June, 2017, Part 2
MEMum presents the second article in a series of three about the recent 12th Invest In ME International Conference (IIMEC12) in London.
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SIV-infected macaques treated with HAART have reduced CNS viral replication...

Discussion in 'XMRV Testing, Treatment and Transmission' started by natasa778, Jul 15, 2010.

  1. natasa778

    natasa778 Senior Member

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    J Infect Dis. 2010 Jul 1;202(1):161-70.

    Simian immunodeficiency virus-infected macaques treated with highly active antiretroviral therapy have reduced central nervous system viral replication and inflammation but persistence of viral DNA.

    Zink MC eta al department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. mczink@jhmi.edu
    Abstract

    BACKGROUND: During the era of highly active antiretroviral therapy (HAART), the prevalence of HIV-associated central nervous system (CNS) disease has increased despite suppression of plasma viremia. METHODS: In a simian immunodeficiency virus (SIV) model system in which all animals develop AIDS and 90% develop CNS disease by 3 months after inoculation, pigtailed macaques were treated with a regimen of tenofovir disoproxil fumarate, saquinavir, atazanavir, and an integrase inhibitor starting at 12 days after inoculation and were euthanized at approximately 175 days after inoculation. RESULTS: Plasma and cerebrospinal fluid (CSF) viral loads declined rapidly after the initiation of HAART. Brain viral RNA was undetectable at necropsy, but viral DNA levels were not different from those in untreated SIV-infected macaques. CNS inflammation was significantly reduced, with decreased brain expression of major histocompatibility complex class II and glial fibrillary acidic protein and reduced levels of CSF CCL2 and interleukin 6. Brain from treated macaques had significantly lower levels of interferon beta, type 1 interferon-inducible gene myxovirus (influenza) resistance A, and indolamine 2,3-dioxygenase messenger RNA, suggesting that immune hyperactivation was suppressed, and fewer CD4(+) and CD8(+) T cells, suggesting that trafficking of T cells from peripheral blood was reduced. Brain levels of CD68 protein and tumor necrosis factor alpha and interferon gamma RNA were reduced but were not significantly lower, indicating continued CNS inflammation. CONCLUSIONS: These data, generated in a rigorous, high-viral-load SIV-infected macaque model, showed that HAART provided benefits with respect to CNS viral replication and inflammation but that no change in the level of viral DNA and continued CNS inflammation occurred in some macaques.
    PMID: 20497048
     
  2. natasa778

    natasa778 Senior Member

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    on the animal model

    more on this animal model of CNS retroviral infection

    J Neurovirol. 2008 Aug;14(4):309-17.

    The accelerated simian immunodeficiency virus macaque model of human immunodeficiency virus-associated neurological disease: from mechanism to treatment.

    Clements JE, Mankowski JL, Gama L, Zink MC.

    Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
    Abstract

    Highly active antiretroviral therapy has been effective in lowering viral loads in the peripheral blood, restoring immune function and reducing the incidence of opportunistic infections and dementia in human immunodeficiency virus (HIV)-infected individuals. However, motor and cognitive deficits and peripheral neuropathy continue, with some studies reporting an increase in prevalence of nervous system disease. The authors developed an accelerated, consistent simian model of HIV infection in which pigtailed macaques are dual inoculated with a neurovirulent simian immunodeficiency virus (SIV) clone and an immunosuppressive SIV strain. Infected animals invariably develop acquired immunodeficiency syndrome (AIDS) and over 90% develop central nervous system disease as well as peripheral nervous system disease with neurodegeneration by 3 months postinoculation. This model provides outstanding opportunities to delineate the pathogenesis of infection, to study the regulation of virus gene expression, and to identify host immune responses throughout the acute, clinically silent and late stages of infection. Using this model, the authors have demonstrated that the virus enters the brain within days after inoculation, that CCL2 (monocyte chemoattractant protein [MCP]-1) plays a major role in recruiting monocytes/macrophages to the brain, and that type I interferons are critical in suppressing early virus replication and inducing viral latency. This model provides a rigorous platform for the testing of potential antiretroviral, immune reconstituting, and/or neuroprotective agents and already has been used to confirm the neuroprotective properties of minocycline, which now is being tested in clinical trials of HIV-infected individuals.

    PMID: 18780232
     
  3. Daffodil

    Daffodil Senior Member

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    so i guess XMRV will cause the same CNS inflammation.....bad news. many patients with HIV and HTLV experience some degree of cognitive impairment.

    aside from minocycline, lithium is supposed to help too.

    i am not sure what it means that there is no viral RNA found but there is viral DNA....can anyone please explain?

    thanks
    sue
     
  4. Lynn

    Lynn Senior Member

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    This is cool. I get to put into use what I just learned in the XMRV seminar. I am sure there are more scientist like people who can answer this, but let me take a stab.

    Dr. Racaniello said the XMRV starts out as viral RNA. Through reverse transcriptase it changes to viral DNA within the body and then is able to insert itself within our own DNA. I would guess that is why they are finding the viral DNA as opposed to RNA in the CNS.

    Okay scientists, did I get that right?

    Lynn
     
  5. Otis

    Otis SeƱor Mumbler

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    Thanks for posting - great reading and by brain can actually absorb most of this today. <<Does anyone else function better mentally with less sleep?>>

    How "valid" is using this neurovirulent clone combined with the immunosuppressive strain? It seems to be geared towards accelerating the neuroinfectiction, but do we know if this combination represents a typical disease state?
     
  6. Angela Kennedy

    Angela Kennedy

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    But this won't be extrapolated to humans, because they're comparing apples and oranges of course...

    That will be an argument put forward so that this research won't support a 'CFS' connection. This sort of thing has been happening with (lyme)borrelliosis for years.

    Meanwhile, another animal model of 'CFS' involves making mice swim for long periods until they start to drown, and putting their tails in painfully hot water for 10 second periods.

    Meanwhile, in the land of human guinea pigs, the scientists can't even sort out a consistent 'CFS' cohort to follow that identified CNS involvement.

    Ah, the advance of science...
     
  7. natasa778

    natasa778 Senior Member

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    Angela, what do you mean by 'it won't be extrapolated to humans'?

    the human model preceded this one, not the other way around (they could not created monkey HIV dementia with HIV, so had to use that one). or do you mean it won't be extrapolated to XMRV/CFS
     
  8. Angela Kennedy

    Angela Kennedy

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    CFS. My argument is that animal testing is not 'good news' for human CFS sufferers, because, in the world of Lyme research, the animal testing has not led to extrapolation to humans. Indeed, animal testing tends to represent a retrograde step in terms of actual progress to getting help in real time for sufferers of illnesses such as Lyme (and relatedly, CFS). And, in a context where there is a phenomenon known as the 'Lyme wars', scientists, I believe and I don't have the references to hand but will try and find them, have said the results from animal testing cannot be extrapolated to humans, in order to deny certain advice or treatment (for example around sexual transmission).

    This opens up a whole can of worms about animal testing in general as an inefficient and rather wasteful way of doing science to benefit 'humans', leaving aside the ethics of it all for this discussion (though we shouldn't generally), and what that means for people with CFS, especially those being asked to fund projects that might involve this sort of testing.

    The problem is that science is not some self-correcting, rational, even logical system that can solve these problems: the CFS situation is a strong example of this problem. I personally would argue that there are ethical issues for both human and animals also, although the widespread ad hominem insinuation of objectors to animal testing as potential animal rights arsonists makes it hard for people to articulate even the actual scientific problems around animal testing, let alone the ethical problems.

    In any case, these issues now look like they are going to come up and bite people in the bum (in a way they might not have before), and ME/CFS advocates need to start thinking about them, hence my bringing them up.
     
  9. ukxmrv

    ukxmrv Senior Member

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    How well does this model work for AIDS?
     
  10. xrayspex

    xrayspex Senior Member

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    well macaques were one of the animals used in the 50 60s to develop vaccines for polio.....and that relates to the theory that AIDs may have been from simian viruses in the vaccines back then so if macaques have the virus and get better w/HAART humans might too?
    Perhaps its no accident that Harvey Alter was presenting in Croatia the power point about xmrv that got leaked to the press....as interestingly I just learned Croatia is one of the countries that Koprowski gave many many children in the 60s his unauthorized and questionable vaccine for polio, he called it CHAT:

    "CHAT was also fed to another eight million children, mainly in Koprowski's homeland of Poland, in Switzerland, Croatia and Sweden, and (on a very small scale) in the United States -- but, crucially, different vaccine pools were used in different places. More important still, I have recently obtained evidence showing that even when the pool numbers were the same, different batches of vaccine were sometimes prepared in different substrates."
    an excerpt from the author on this topic Edward Hooper who wrote The River: A Journey to the Source of HIV and AIDS. Allen Lane/Penguin Press, 1999 i
    http://www.uow.edu.au/~bmartin/dissent/documents/AIDS/refs.html

    anyone know the update on all this?? Something I found from him in 2000 made it sound like it was still up in the air, there were some good reviews of his book but also scientists trying to discredit him, I guess in order to figure out if vaccines started human aids scientists would need to test Koprowski's remaining samples of CHAT, but he was trying to get out of that and they were trying to say it was hunters and monkeys blood meshing in the bush of africa that started aids, but I see him refer to a NIH guy that we find questionable in the above linked article, Hooper excerpt:

    "What I find disturbing about all this is that it represents science by press conference. In the bid to present the information in an accessible form for the media, statements get ever more simplified, claims ever more grandiose. This, I would propose, is not the best way to arrive at the truth. Shortly after the Korber speech, Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases, the man effectively heading AIDS research in the US, was going several steps further, opining that Korber's findings would 'end any speculation about a link between the HIV-1 pandemic and the African polio vaccine initiatives, "... at least among scientists".' (fauci protecting koprowski and advocating hunter/monkey aids theory in 2000)

    Hooper also writes in the article in the link I provided about early aids and vaccine correlaton with koprowski:

    By contrast, within sub-Saharan Africa, there are many retrospective traces of HIV-1 (beginning with the Leopoldville blood sample of 1959), and of HIV-1-related AIDS. Significantly, nearly all of them pertain to the Congo, Rwanda and Burundi. Not only that, but a comparison of the specific towns, villages and rural areas where CHAT was fed, and those places where HIV and AIDS subsequently appeared, reveals some quite stunning correlations.

    In the years up to and including 1980 (the year before AIDS was first recognized in America), there were 38 confirmed or probable cases of HIV-1-related AIDS from Africa, of which 31 pertain to these three countries, and another four to towns lying close to their borders. We have an identifiable town of domicile (or else likely town of infection) for 28 of these early AIDS cases, and 64% of them come from towns where CHAT was fed, and 82% from towns within 175 miles of places where CHAT was fed. For a disease like AIDS with a long latency period (which allows more time for an infectee to move away from the site of infection), the synchronicity of time and place is remarkable.

    If one looks instead at proven samples of HIV-1-positive blood taken in Africa in 1980 or before, the correlations with the Koprowski vaccine become even more compelling. Over 87% of the 39 positive African samples from 1980 or earlier come from towns where CHAT was fed. And 100% come from places within 90 miles of CHAT vaccination sites (See Figures 1 and 2). (go to the link for charts)
    --------------
    wow go read the link, hooper also says:
    "It is, in short, not unreasonable to propose that some of the CHAT batches fed in central Africa between 1957 and 1960 could have been prepared in chimp tissue -- either in the US, Belgium or the Congo itself -- and that some of this tissue may have been infected with the simian precursor of HIV-1."
    Which made me think of kenny de merleir, are there lots of cases of weird retorviral stuff where he is cus of that bad batch of macaque vaccines CHAT from koprowski they got in belgium??
     
  11. natasa778

    natasa778 Senior Member

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    Interesting that you mention that, I was chatting to someone from Croatia the other day who grew up on an estate - a street had lots of kids, he was saying how remarkably there was a large number of them with mental retardation (not autism, not a single one, but severe 'straight forward' retardation). This person was born 1964 and interestingly ALL those affected kids were around his age group.

    To go back even further, Zagreb Croatia had a strong pharma presence and a fully fledged vaccine program in the 40s and even before that. My mum and her siblings grew up there. That side of my family has MS, lymphoma cancer, neuropathy, autism, CFS, allergies, speech delays/dyslexia ...
     
  12. xrayspex

    xrayspex Senior Member

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    wow, that is very interesting
    Tom Curtis and Edward Hooper are the bomb on this topic, I dont know what happened to them or their research but I have a feeling Fauci made it go away.....
    I also want to know why Elaine Defreitas was working for Koprowski's org Wistar, if thats an accident/coincidence but her findings were relevent to him or his cohorts and thus was was made to go away.....
     

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