Hello Theodore and friends.
The following thoughts of mine may be of interest to some of you.
Before my speculation party...
The specific juicy bit for me from this new December 2016 De Meirleir et al paper, personally, is the following:
''Lastly, we BLASTed the 233 random peptides identified by RF against the proteomes of viruses and bacteria known to infect humans. The most prevalent viral hit was to the gp120 protein of human immunodeficiency virus 1. This sequence was homologous to the conserved motif; therefore, it is likely the result of cross-reactivity to antibodies raised to HERVs or another similar sequence. Of the bacterial hits that have been previously associated with ME, the type IV secretion protein Rhs of H. alvei was identified in our search. H. alvei is Gram-negative, facultative anaerobic intestinal bacteria. A previous study by Maes et al. reported that ME cases have elevated serum IgA and IgM antibodies, to H. alvei, that likely result from intestinal bacterial translocation''.
gp120 isn't a Formula 1 motor race, but an envelope protein of HIV human retrovirus.
Note they say the following regarding Rv's (repeat of above).
''This sequence was homologous to the conserved motif; therefore, it is likely the result of cross-reactivity to antibodies raised to HERVs or another similar sequence''
In other-words the ME researchers are practically dismissing HIV involvement but not another HERV, which is logical and sensible at the point in time.
Referencing HERV's then has potential to correlate with theories or anecdotal preliminary evidence (unpublished) that ME is indeed associated to retroviruses (HERV's - of unknown cause why they become pathogenic) and these same infections are found in other autoimmune illnesses affecting neurology, such as Multiple Sclerosis:
MS patient walks after taking HIV drugs
Source:
http://www.bbc.co.uk/news/uk-england-sussex-34659771
Could HIV drugs help treat MS?
http://www.nhs.uk/news/2014/08August/Pages/HIV-drugs-could-treat-multiple-sclerosis.aspx
HIV and lower risk of MS revealed
Source:
http://jnnp.bmj.com/content/early/2014/07/16/jnnp-2014-307932.long
Now we also know there is some evidence for not just MS, but also HIV and HERV's being linked, because:
HIV is associated to HERV production:
''Infection of humans with the retrovirus HIV-1 has profound effects upon the resident, endogenous retroviruses. Transcripts and proteins representing diverse classes of endogenous retroviruses are upregulated''.
HIV infection and HERV expression: a review
Source: Kuyl, A. 2012
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3311604/
And by another group 3 years later....
''Our results demonstrate that HIV-1 can alter HERV transcription patterns of infected cells and indicate a correlation between activation of HERV elements and the level of HIV-1 production. Moreover, our results suggest that the effects of HIV-1 on HERV activity may be far more extensive and complex than anticipated from initial studies with clinical material.''
Modulation of human endogenous retrovirus (HERV) transcription during persistent and de novo HIV-1 infection
Source: Vincendeau et al, 2015
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375885/
Moving away from RV's for a moment to the stomach bacteria ideas we've all been hearing of in vague snippets of research. Well if people (who haven't tested their own 'gut flora') were skeptical I wouldn't be, as bacteria in the stomach is now being associated to 'hardcore' degenerative neurological diseases like PD never mind ME.
Parkinson's disease appears to be connected to Bacterial translocation in the gut:
Source:
http://www.bbc.co.uk/news/health-38173287
Back to RV's and getting very hypothetical, but please hear me out just in case there is some vague link to my thoughts:
I spotted
Sphigomyelin was mentioned by Dr Navieux regarding the recent Mitchocondrial blood test that is being researched in CFS in America and this was one of the analytes I believed measured in a 'test' that appears to be available for a sizeable cost (cost helps to fund research) privately on an experimental basis at least.
Well people with long memories, may recall that the twin girls with 'XMRV' (not XMRV but maybe another RV) have ultra rare childhood Alzheimer's -
Niemann-Pick disease Turns out Neiman Pick is associated to Sphigomyelin deficiency.
Source:
http://nnpdf.org/the-disease/overview/
And? Well shouldn't RV's be associated to Sphigomyelin then if the twin girls who had the dud XMRV assay maybe had
another RV?
Well look what I discovered. Sphingolipid defects
are associated to an RV: HIV-1 to be exact.
(NB: Neiman Pick if I remember correctly causes hyper cholesterol) and of note XMRV is directed by cholesterol.
'
' Depletion of cholesterol from XMRV-infected cells significantly reduced virus release, suggesting that cholesterol and intact lipid rafts are required for the budding process of XMRV. These results suggest that unlike glycoproteins of other retroviruses, the association of XMRV glycoprotein with virions is highly dependent on cholesterol and lipid rafts''.
Cholesterol Depletion Inactivates XMRV and Leads to Viral Envelope Protein Release from Virions: Evidence for Role of Cholesterol in XMRV Infection
Source: Tang et al, 2012
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0048013
Also note, 3 years before that published paper, the twin girls parents were discussing this on their own charity website:
Does XMRV Use Cholesterol to Survive in the Body Like HIV-AIDS? What XMRV Infected Twins May Teach us about the Virus.
Source:
http://addiandcassi.com/does-xmrv-u...fected-children-may-teach-us-about-the-virus/
Hence it was logical for Mikovits to test the girls for XMRV (wrong name) and it was positive - because it wasn't XMRV it was something else....not contamination as it's the sick people who test positive at far higher rates - if the lab was contaminated all people would test positive, or there wouldn't be a 20 fold slide to people with a neuro disease testing positive - that's the smoking gun at the end of the day - simtaneously after claiming to the public retroviruses don't exist in CFS via the botched Lipin/Alter CFS study the US blood safety groups behind closed doors used this company to clean US blood donors blood of potential retroviruses (2011 onwards). A most curious decision if no retroviruses were found - why waste millions of dollars on money on pointless technology said only to be needed by a 'fradulent researcher'? So that's all we needed to know. She found something in CFS, not XMRV Silverman, something else...
http://interceptbloodsystem.com/blood-center/intercept
So now it might get really interesting RE: GP120 of the new December 2016 De Meirleir finding, Dr Davis/Navieux, Fluge & Mella and ME regarding the following in retroviral disease:
Inhibition of Sphingolipid Biosynthesis Reduces HIV-1 Infectivity.
Source: Brugger et al, 2005
http://www.pnas.org/content/103/8/2641.full
We propose that sphingomyelinase inhibits HIV
Source: Finnegan et al, 2007
http://jvi.asm.org/content/81/10/5294.full
Sphingomyelin synthase 2, but not sphingomyelin synthase 1, is involved in HIV-1 envelope-mediated membrane fusion.
Source: Hayashi et al, 2014
So now we are linking a neurogenerative disease and HIV dementia, and in addition abnormal prion protein production and HIV GP120
A common sphingolipid-binding domain in HIV-1, Alzheimer and prion proteins
Link to PDF with interesting diagram:
http://journals.cambridge.org/fulltext_content/ERM/ERM4_27/S1462399402005392sup011.pdf
The text reads:
'' A common sphingolipid-binding domain in HIV-1, Alzheimer and prion proteins. The lateral chains of the residues of pathologically important proteins known to be involved in binding to glycosphingolipids and sphingomyelin in plasma membranes are shown.
+
''The human immunodeficiency virus 1 gp120 V3 loop. (b) The β-amyloid peptide 1–40, involved in Alzheimer’s disease. (c) Comparison of the wild-type (wt) human PrP with the E200K mutation, which is associated with familial Creutzfeldt–Jakob disease; this mutation might impair the association of the mutated PrPC with raft lipids such as sphingomyelin through electrostatic repulsion between the positive charges of sphingomyelin and of the lysine (K) residue''.
'The V3-like domain of PrP is a disulfide-linked loop (Cys(179)-Cys(214)) that includes the E200K mutation site associated with familial Creutzfeldt-Jakob disease. This mutation abrogated sphingomyelin recognition. The identification of a common sphingolipid-binding motif in gp120, PrP, and beta-amyloid peptide underscores the role of lipid rafts in the pathogenesis of HIV-1, Alzheimer, and prion diseases and may provide new therapeutic strategies.''
Identification of a common sphingolipid-binding domain in Alzheimer, prion, and HIV-1 proteins.
Source: Mahfoud et al, 2002
https://www.ncbi.nlm.nih.gov/pubmed/11792705
''Human immunodeficiency virus type 1 (HIV-1) infection is known to cause disorders of the CNS, including HIV-associated dementia (HAD). HIV-1 coat protein gp120 (glycoprotein 120) induces neuronal apoptosis and has been implicated in the pathogenesis of HAD. However, the mechanism by which gp120 causes neuronal apoptosis is poorly understood.''
Human Immunodeficiency Virus Type 1 gp120 Induces Apoptosis in Human Primary Neurons through Redox-Regulated Activation of Neutral Sphingomyelinase
Source: Jana & Pahan, 2004.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1955476/
Why mention the prions and ME if the above is about vCJD/HIV?
Well from my links above we have learn't that HIV can interfere with HERV's and also HERV's are associated to autoimmune diseases such as MS and ME is increasingly linked to Autoimmunity, and perhaps even HERV's now also - or will be. If you read the research on the above, then prions are associated to all three, regarding gp120 which cropped up in this De Meirleir et al, recent study.
So why is this relevant to ME?
Because KDM also found, in severely affected especially, PrPC in blood (using an experimental assay) is abnormally low - practically zero left - and in saliva, misfolded prions are detected in ME sufferers. No published work to my knowledge, but some basic information here.
Taken in combination this may all link as PrPC is neuroprotective, specifically against oxidative stress, and oxidative stress is associated to CFS biological research, including some neuroimaging studies that seem to show accelerated ageing of the brain, with changes in 'matter' volume and in the Nakatomi paper, neuroinflammation damage.
Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An ¹¹C-(R)-PK11195 PET Study.
Source:
https://www.ncbi.nlm.nih.gov/pubmed/24665088
It thus wouldn't be a surprise to find some form of HERV retrovirus/autoimmunity/infections driving ME all along - perhaps rather like MS and perhaps like element of HIV dementia (remember decades ago, Dr Paul Cheney's comment that a doctor in his Hospital mistook CFS brain scans for AIDS patients?).
I think somewhere in all this I've posted there is something of some interest towards CFS, ME, HIV and Dementia, with the whole point of my post suggesting HERV's may well be involved and it's not just KDM's group thinking along this line.[/quote]