XMRV Link Gives False Hope for CFS

FunkOdyssey

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The evidence is the clinical response to antibiotics. Symptoms should not change like they do.
I guess there's no way the Marshall Protocol's favorite antibiotic, minocycline, could benefit someone with a retroviral infection....

J Infect Dis. 2010 Apr 15;201(8):1132-40.
Minocycline attenuates HIV infection and reactivation by suppressing cellular activation in human CD4+ T cells.

Szeto GL, Brice AK, Yang HC, Barber SA, Siliciano RF, Clements JE.
Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Treatment of human immunodeficiency virus (HIV) infection with highly active antiretroviral therapy (HAART) is effective but can be associated with toxic effects and is expensive. Other options may be useful for long-term therapy. The immunomodulatory antibiotic minocycline could be an effective, low-cost adjunctive treatment to HAART. Minocycline mediated a dose-dependent decrease in single-cycle CXCR4-tropic HIV infection and decreased viral RNA after infection of CD4+ T cells with HIV NL4-3. Reactivation from latency was also decreased in a primary CD4+ T cell-derived model and in resting CD4+ T cells from HIV-infected patients. Minocycline treatment resulted in significant changes in activation marker expression and inhibited proliferation and cytokine secretion of CD4+ T cells in response to activation. This study demonstrates that minocycline reduces HIV replication and reactivation and decreases CD4+ T cell activation. The anti-HIV effects of minocycline are mediated by altering the cellular environment rather than directly targeting virus, placing minocycline in the class of anticellular anti-HIV drugs.

PMID: 20205570
Brain Res. 2009 Aug 25;1286:174-84. Epub 2009 Jun 11.
Attenuation of oxidative stress, inflammation and apoptosis by minocycline prevents retrovirus-induced neurodegeneration in mice.

Kuang X, Scofield VL, Yan M, Stoica G, Liu N, Wong PK.
Department of Carcinogenesis, University of Texas, M.D. Anderson Cancer Center, Science Park-Research Division

The ts1 mutant of the Moloney murine leukemia virus (MoMuLV) causes neurodegeneration in infected mice that resembles HIV-associated dementia. We have shown previously that ts1 infects glial cells in the brain, but not neurons. The most likely mechanism for ts1-mediated neurodegeneration is loss of glial redox support and glial cell toxicity to neurons. Minocycline has been shown to have neuroprotective effects in various models of neurodegeneration. This study was designed to determine whether and how minocycline prevents paralysis and death in ts1-infected mice. We show here that minocycline delays neurodegeneration in ts1-infected mice, and that it prevents death of cultured astrocytes infected by ts1 through attenuating oxidative stress, inflammation and apoptosis. Although minocycline reduces virus titers in the CNS of infected mice, it does not affect virus titers in infected mice thymi, spleens or infected C1 astrocytes. In addition, minocycline prevents death of primary neurons when they are cocultured with ts1-infected astrocytes, through mechanisms involving both inhibition of oxidative stress and upregulation of the transcription factor NF-E2-related factor 2 (Nrf2), which controls cellular antioxidant defenses. We conclude that minocycline delays retrovirus ts1-induced neurodegeneration involving antioxidant, anti-inflammation and anti-apoptotic mechanisms.

PMID: 19523933
J Neurovirol. 2008 Oct;14(5):376-88. Epub 2008 Nov 12.
Mechanisms of minocycline-induced suppression of simian immunodeficiency virus encephalitis: inhibition of apoptosis signal-regulating kinase 1.

Follstaedt SC, Barber SA, Zink MC.
Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

Human immunodeficiency virus (HIV) infection of the central nervous system (CNS) can lead to cognitive dysfunction, even in individuals treated with highly active antiretroviral therapy. Using an established simian immunodeficiency virus (SIV)/macaque model of HIV CNS disease, we previously reported that infection shifts the balance of activation of mitogen-activated protein kinase (MAPK) signaling pathways in the brain, resulting in increased activation of the neurodegenerative MAPKs p38 and JNK. Minocycline treatment of SIV-infected macaques reduced the incidence and severity of SIV encephalitis in this model, and suppressed the activation of p38 in the brain. The purpose of this study was to further examine the effects of minocycline on neurodegenerative MAPK signaling. We first demonstrated that minocycline also decreases JNK activation in the brain and levels of the inflammatory mediator nitric oxide (NO). We next used NO to activate these MAPK pathways in vitro, and demonstrated that minocycline suppresses p38 and c-Jun N-terminal kinase (JNK) activation by reducing intracellular levels, and hence, activation of apoptosis signal-regulating kinase 1 (ASK1), a MAPK kinase capable of selectively activating both pathways. We then demonstrated that ASK1 activation in the brain during SIV infection is suppressed by minocycline. By suppressing p38 and JNK activation pathways, which are important for the production of and responses to inflammatory mediators, minocycline may interrupt the vicious cycle of inflammation that both results from, and promotes, virus replication in SIV and HIV CNS disease.

PMID: 19003592
Bioinformatics. 2007 Oct 15;23(20):2797-9. Epub 2007 Sep 5.
Identification of potential HIV-1 targets of minocycline.

Jenwitheesuk E, Samudrala R.
National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency

Minocycline, a broad spectrum antibiotic, has been discovered to have inhibitory activity against HIV-1 in vitro, but the targets inhibited are unknown. We used a docking with dynamics protocol developed by us to predict the binding affinities of minocycline against seven active sites of five HIV-1 proteins to putatively identify the potential target(s) of minocycline. The results indicate that minocycline has the highest predicted binding affinity against HIV-1 integrase.

PMID: 17804437
PLoS One. 2010 May 7;5(5):e10523.
Proton magnetic resonance spectroscopy reveals neuroprotection by oral minocycline in a nonhuman primate model of accelerated NeuroAIDS.

Ratai EM, Bombardier JP, Joo CG, Annamalai L, Burdo TH, Campbell J, Fell R, Hakimelahi R, He J, Autissier P, Lentz MR, Halpern EF, Masliah E, Williams KC, Westmoreland SV, Gonzlez RG.
AA Martinos Center for Biomedical Imaging and Neuroradiology Division, Massachusetts General Hospital

BACKGROUND: Despite the advent of highly active anti-retroviral therapy (HAART), HIV-associated neurocognitive disorders continue to be a significant problem. In efforts to understand and alleviate neurocognitive deficits associated with HIV, we used an accelerated simian immunodeficiency virus (SIV) macaque model of NeuroAIDS to test whether minocycline is neuroprotective against lentiviral-induced neuronal injury.

METHODOLOGY/PRINCIPAL FINDINGS: Eleven rhesus macaques were infected with SIV, depleted of CD8+ lymphocytes, and studied until eight weeks post inoculation (wpi). Seven animals received daily minocycline orally beginning at 4 wpi. Neuronal integrity was monitored in vivo by proton magnetic resonance spectroscopy and post-mortem by immunohistochemistry for synaptophysin (SYN), microtubule-associated protein 2 (MAP2), and neuronal counts. Astrogliosis and microglial activation were quantified by measuring glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (IBA-1), respectively. SIV infection followed by CD8+ cell depletion induced a progressive decline in neuronal integrity evidenced by declining N-acetylaspartate/creatine (NAA/Cr), which was arrested with minocycline treatment. The recovery of this ratio was due to increases in NAA, indicating neuronal recovery, and decreases in Cr, likely reflecting downregulation of glial cell activation. SYN, MAP2, and neuronal counts were found to be higher in minocycline-treated animals compared to untreated animals while GFAP and IBA-1 expression were decreased compared to controls. CSF and plasma viral loads were lower in MN-treated animals.

CONCLUSIONS/SIGNIFICANCE: In conclusion, oral minocycline alleviates neuronal damage induced by the AIDS virus.

PMID: 20479889
A novel use for an old drug: the potential for minocycline as anti-HIV adjuvant therapy.

Copeland KF, Brooks JI.

J Infect Dis. 2010 Apr 15;201(8):1115-7. No abstract available. PMID: 20205572
JAMA. 2005 Apr 27;293(16):2003-11.
Neuroprotective and anti-human immunodeficiency virus activity of minocycline.

Zink MC, Uhrlaub J, DeWitt J, Voelker T, Bullock B, Mankowski J, Tarwater P, Clements J, Barber S.
Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, Md 21205, USA. mczink@jhmi.edu

CONTEXT: The prevalence of human immunodeficiency virus (HIV) central nervous system (CNS) disease has not decreased despite highly active antiretroviral therapy. Current antiretroviral drugs are expensive, have significant adverse effects including neurotoxicity, and few cross the blood-brain barrier.

OBJECTIVE: To examine the ability of minocycline, an antibiotic with potent anti-inflammatory and neuroprotective properties, to protect against encephalitis and neurodegeneration using a rapid, high viral load simian immunodeficiency virus (SIV) model of HIV-associated CNS disease that constitutes a rigorous in vivo test for potential therapeutics.

DESIGN AND SUBJECTS: Five SIV-infected pigtailed macaques were treated with 4 mg/kg per day of minocycline beginning at early asymptomatic infection (21 days after inoculation). Another 6 macaques were inoculated with SIV but remained untreated. Blood and cerebrospinal fluid (CSF) samples were taken on days 7, 10, 14, 21, 28, 35, 43, 56, 70, 77, and 84, and all macaques were humanely killed at 84 days after inoculation, a time that corresponds to late-stage infection in HIV-infected individuals.

MAIN OUTCOME MEASURES: Blood and CSF samples were tested for viral load by real-time reverse transcription-polymerase chain reaction and levels of monocyte chemoattractant protein 1 were quantitated by enzyme-linked immunosorbent assay. The presence and severity of encephalitis was determined by microscopic examination of tissues. Central nervous system inflammation was further assessed by measuring infiltration and activation of macrophages, activation of p38 mitogen-activated protein kinase and expression of amyloid precursor protein by quantitative immunohistochemistry.

RESULTS: Minocycline-treated macaques had less severe encephalitis (P = .02), reduced CNS expression of neuroinflammatory markers (major histocompatibility complex class II, P = .03; macrophage marker CD68 , P = .07; T-cell intracytoplasmic antigen 1, P = .03; CSF monocyte chemoattractant protein 1, P = .001), reduced activation of p38 mitogen-activated protein kinase (P<.001), less axonal degeneration (beta-amyloid precursor protein, P = .03), and lower CNS virus replication (viral RNA, P = .04; viral antigen, P = .04). In in vitro analysis, minocycline suppression of HIV and SIV replication in cultured primary macrophages did not correlate with suppression of activation of p38-mitogen-activated protein kinase pathways, whereas suppression in primary lymphocytes correlated with suppression of p38 activation.

CONCLUSIONS: In this experimental SIV model of HIV CNS disease, minocycline reduced the severity of encephalitis, suppressed viral load in the brain, and decreased the expression of CNS inflammatory markers. In vitro, minocycline inhibited SIV and HIV replication. These findings suggest that minocycline, a safe, inexpensive, and readily available antibiotic should be investigated as an anti-HIV therapeutic.

PMID: 15855434
 

free at last

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Lol it seems antibiotics can then

The one thing that strikes me about most discussions and insights about this illness ( including my own experiances ) is the contradicting nature of evidence from patient to patient. as i recovered a lot of my health ( but still get symptoms ) and i neither took prolonged use of antibiotics anti virals avoided mold ect. All i took was evening primrose vit c. multi vits. magnesium, calcium cod liver oil. And not always the whole lot, just when i could get them. Restoring sleep patterns with the drowsy knockout effect of amitriptylene helped stop the deteriation.

But didnt stop the illness or symptoms. Only years of rest, inactivety, good sleep. the supplements mentioned. Lots of raw vege ( many many different types ) raw galic. seemed to help a very slow but progressive calming of symptoms. Im sure it was Dr Peterson who said ( might be wrong ) apologies no link. That its possible for some that the immune system stops reacting to the xmrv virus, producing less symptomatic flares. But the long term effects of the immune system doing this are uncertain.

Maybe this explains why there are healthy xmrv populations. Maybe if the immune system does not see the virus as a threat and doesnt continually keep mounting intermitent attacks. Then symptoms are just not present. in my case i belive its possible i had xmrv many years before i got ill. But through a series of many many infections, maybe both viral and bacterial, My immune system started to attack xmrv, and a cycle of repeated immune responses, with relative inactivety of the immune system at times of less symptom periods. really caused a type of off and on immune type of disfunction to occur for many years ( about 16 now )
I have no real understanding of how these things work, and if im way off base, apologies to all for trying to input here. But these ideas seem to make sense to me personally.

Maybe over time, without even trying particulaly, just the things mentioned i was doing. my immune system learned to re train itself to a time when ( like the healthy xmrv people ) symptoms are not on a continual basis anymore. I have just had a very long period lasting 3 or 4 months that symptoms were hardly happening at all. But recently out of the blue for no apparent reason. they came back. And its been like that now for years. It seems very unpredictable, for how long good periods will last, or how often the worse periods will come again.

I look for triggers, and sometimes it seems excercise can be a trigger, but not always. I feel often there can be many different types of triggers. and blame everything. other times i think, the fine line is so delicate, it really will just keep coming back no matter what i do, or do not do. And i think this will be true for most here.

But for sure, compared to the past CFS/ME symptoms ( maybe xmrv symptoms ) have shown a very gradual improvement in both frequency of attacks, and severity of symptoms themsleves. Anything that can effect the chemical and immune functions of the body seem to have a potential to upset this very fine delicate balancing act.of symptom, or symptomless periods of time.

Alcohol even very small amounts can. Pot in my experiance is very very bad, and mild continual use produces more frequent and of a higher strength symptom flare up, ( but others have found it helps ? ) so much so, i no longer touch it. I belive it can produce a over active immune system in some, and possibly a underactive immune system in others, possibly explainling the contradiction from pateint to patient here.

I apologoze i have no links, and is only a personal experiance, and somewhat guesswork. those that choose to ignore guesswork, i fully understand.

I dont belive any one theory fits all for this disease, is the answer. Not bacteria, mold. viruses chemicals ect. I think its all relevent. But as for example, i didnt do any particular mold avoidence or antibiotic treatment, antiviral drugs ect. yet i still got profound improvement of my health over the years. doing what i described earlier.

Some may say mold is at the top of there list, or bacteria treatment. But i dont think that fits my personal experiance, even if it fits other peoples. who knows maybe one day we will find a reason for this particular discrepency But i dont believe im the only one. And i do belive mold is bad, and cause flare ups. but to say its at the top of the list
just doesnt feel right, and doesnt really seem to fit my particular experiance, even if it does others. Same for the MP bacteria theory. relevent yes. the answer for us all probably not.

But to say i dont fit the correct diagnosis based on that experiance is others guesswork, and i could lay the same question to them. All i will say is, i was diagnosed CFS by good ole Wessley, and another psychiatrist. A consultant at greenwich hospital, and proff Findley harold wood hospital both agreed ME/CFS i fitted many of the symptoms canadian concensus criteria. so i havent a clue, But watch out for personal beliefs, as they may only fit a subset, and we are right back at you never had ME in the first place mentality. Wessley isnt the only one to doubt patient testimony, based on personal experiance or beliefs i dont belive. If you ask me my fav theory for a lot of this, based on what ive learned this last year, and my expriances. I will say xmrv is at the top of the list. with all the other stuff co factors but still relevent hand in hand with that little beauty. Time will tell i suppose. My heart goes out to all of you that struggle with this complex and conradictory disease. Watching us all go round and round, looking for a answer and a future cure. It just sucks. But we must do it.
 

FunkOdyssey

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Actually my point was that it might be a very good idea, and were you to take a drug like minocycline, improvement in your condition would NOT necessarily mean that you had a bacterial infection. These drugs do other things, helpful things, totally unrelated to antibacterial activity. That's why it can be used as an adjunct treatment in HIV.
 

Jemal

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I took doxycycline, an antibiotic which falls in the same group as minocycline, and I definitely noted improvement. Some improvement seems to be lasting, even though I am not taking doxycycline anymore.

The big question is though: is the immune system doing good by attacking XMRV? This conflict seems to cause a lot of symptoms. If XMRV doesn't cause symptoms of its own, then the immune reaction is pretty much unwanted. But if XMRV causes things like cancer, the immune response might be a blessing and then you might not want to stop this response.
 

xrayspex

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jemal thats interesting, one of the factors right before my big demise 20ish years ago, was I was taking erythomyocin for skin stuff and it was really hurting my gut, and a couple other meds that summer seemed to create a bad cocktail where things went from bad to worse.....but I have regretted that erythomyocin, they used to hand it out like candy and I was really apparently healthy and fit before that but in retrospect I think I probly already had xmrv dormant