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MulV model of AIDS and cardiac dysfunction + alcohol intolerance in CFS?

Discussion in 'XMRV Research and Replication Studies' started by natasa778, Oct 6, 2010.

  1. natasa778

    natasa778 Senior Member

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    London UK
    MURINE RETROVIRUS INFECTION AND THE EFFECT OF CHRONIC ALCOHOL CONSUMPTION: PROTEOMIC ANALYSIS OF CARDIAC PROTEIN EXPRESSION

    http://alcalc.oxfordjournals.org/content/38/2/103.full

    some highlights:

    Aims: The cardiovascular complications of acquired immunodeficiency syndrome (AIDS) are serious, including the occurrence of pathological heart conditions such as cardiomyopathy. Chronic alcohol consumption accentuates the severity of AIDS and may contribute to the development of cardiomyopathy. The aim of this work was to use a proteomics approach to investigate global alterations in protein expression in a mouse model of AIDS in the presence or absence of chronic alcohol consumption. ... Results: A number of specific proteins were observed to be differentially expressed in the mouse heart due to the effect of ethanol feeding alone. Differentially expressed proteins were also observed that were due to viral infection alone. Ethanol feeding and viral infection appeared to have similar effects on the expression of a number of proteins. A total of 24 proteins were altered by infection alone. Of these 24 proteins, eight were affected by alcohol, with six alterations being ameliorated and two being exacerbated by alcohol. Two of these proteins have been identified as the 27 kDa heat-shock protein and mitochondrial long-chain acyl-CoA thioesterase 1. Conclusions: These results suggest that chronic alcohol consumption may exacerbate the effects of viral infection on the heart by lowering the stress response leading to de-protection and further cytotoxic effects.

    INTRODUCTION
    in this study, we used a proteomic approach to investigate a murine model of acquired immunodeficiency syndrome (AIDS) induced by LP-BM5 leukaemia virus (MuLV). LP-BM5 MuLV-infected mice characteristically develop hypergamma-globulinaemia, splenomegaly, lymphadenopathy, T-cell functional deficiency, B-cell dysfunction, and, in the later stages, neurological signs including paralysis as well as susceptibility to opportunistic infections (Liang et al., 1996). The similarities between murine AIDS and human AIDS are striking, with similar changes in immune functions, T-cell differentiation, cytokine production, disease resistance and oxidative stress.



    DISCUSSION

    The murine model of AIDS induced by LP-BM5 leukaemia virus displays a number of features of human AIDS (Liang et al., 1996), and has been a useful tool for the investigation of retrovirus-induced immunodeficiency and the effects of ethanol as an accelerating cofactor (Fitzpatrick et al., 1995). This study represents the first proteomic analysis of global protein alterations in the murine model of AIDS induced by LP-BM5 leukaemia virus. Using a proteomic approach, we have demonstrated that the expression of a number of cardiac proteins is significantly altered upon viral infection

    As might be expected, the comparison of the uninfected and infected, ethanol-treated mice (which indicated spots altered due to infection or ethanol or a combined effect of ethanol and infection) produced the largest number of protein expression changes 53 proteins were reduced and 15 were increased in the infected, ethanol-treated group. In a number of cases, the effect of infection mirrored that of alcohol. In most cases, the effect of the combination of alcohol and infection did not increase or decrease the effect of either treatment in isolation. Such examples are spots 536 and 482 shown in Fig. 2. It is not clear why this should be the case, but it is possible that these proteins may be part of the stress response, which may be activated in a similar fashion by both infection and alcohol feeding.

    It is interesting to note that, of the 24 proteins shown to be altered in expression in the heart due to LP-BM5 infection alone, eight appeared to be further altered by ethanol feeding. However, of these eight proteins, the majority (six) were ameliorated by ethanol and for only two was the effect of infection exacerbated by ethanol. This may appear to indicate that alcohol could produce a level of cardiac protection from the virus, which would perhaps contradict the tenet that ethanol consumption aggravates the effects of AIDS. However, if these proteins represent part of a protective response to viral infection it is possible that the effect of alcohol consumption may lead to a de-protection of the cardiac myocyte and a consequent aggravation of the effects of infection. Indeed, one of the proteins altered in response to ethanol feeding was identified as the 27 kDa HSP27. It is possible, therefore, that ethanol consumption may accentuate the effects of retroviral infection in the heart by down-regulating the antiviral response and thereby compromising the ability of the cardiac myocyte to protect itself against the effect of viral damage.
  2. pamb

    pamb Senior Member

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    Edmonton, AB, Canada
    Most interesting and a great find at this point in the research. But of course also confusing to the not scientifically inclined.

    Just adding a 'me-to' re: alcohol. My CCC husband (I'm the healthy caregiver) used to love his wine, now just a few swallows and he is just like Diesel "head gets red, malaise starts very soon and no positive effect".

    We've been telling Dr's about this weirdness since very early in John's history with ME/CFS and none have had any idea. It would be amazing if there is some clear, or relatively clear connection here. I wonder if this might be something that could help with a causal connection? Of course I only understood about 25% of the article so may be way off base.
  3. Cort

    Cort Phoenix Rising Founder

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    Really fascinating - the alcohol intolerance problem is CFS seems to be a real hallmark of it - and has to be explained one way or another; this is the first time I've ever seen anybody try.

    Lets find out just how common this mysterious alcohol intolerance is. Take the Alcohol Tolerance poll here.
  4. Cort

    Cort Phoenix Rising Founder

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    This is the kind of thing that, if this disease was well studied researchers would have looked at - and it would lead to something. Its a strange thing! Does alcohol intolerance occur in any other disorders?
  5. Countrygirl

    Countrygirl Senior Member

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    When many of our farmers in South West England became ill with sheep dip 'flu and developed the symptoms of M.E. through organophosphate poisoning they too became alcohol intolerant.

    I have found that after about 25 years of being very alcohol intolerant I can now drink a glass of dry white wine without a problem. Do other M.E. veterans find that after many years their alcohol intolerance improves?

    C.G.
  6. helsbells

    helsbells Senior Member

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    My alcohol intolerance extends to being near someone whos drunk heavily. If my partner has been out at the weekend and drank heavily with friends he has to sleep in a different room as the fumes make me ill. A good few years ago now and a little better than I am now i went in denial and decided I could drink cider - thinking it was purer than some drinks. needless to say it didn't last long but one weird thing i did notice. In my youth i was drunk quite easily, a couple of pints and I was nicely toasted but when i was drinking "ill" i actually didn't seem to get drunk at all. hardly scientific as I only did it on about 3 occasions before facing the fact it made me much worse (as i say i was a little better then too) but the not getting drunk think was weird.
  7. xrayspex

    xrayspex Senior Member

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    u.s.a.
    never had a tolerance but it was much worse even after afflicted to now where even sips make me feel cruddy, if I have half glass wine my gut will feel punched out the next day, so dont do it of course. although I did have a small glass of wheatfree beer from a friend this summer and nothing bad happened, shocking.
    but makes me wonder though if the recurring mono I had as teen was the start of cfs and why I was such a fool on just a few beers in h.s.
  8. HowToEscape?

    HowToEscape? Senior Member

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    Re alcohol intolerance: I have the alcohol intolerance here and thought it very odd, as noted it is not uncommon with us. It's note in Enlander's patient/family handbook on what was then called CFS.

    The effect varies: at times a few sips will knock me down, during remissions I can handle 1/2 glass alone or a full glass with meals. But that's the exception; mostly (90%) of the time, a couple ounces of wine can cost 1-3 hours. The mention of heat stress is interesting, because the sensations are very much like those from taking a shower or bath, with knocks me down with nearly 100% reliability.
    Alcohol and heat - especially via water (bath/shower) tolerance should probably be secondary markers for M.E. When they occur along with PEM and brain fog and blood pressure/volume issues when upright I'd say to strongly consider a diagnosis of M.E.

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