XMRV CFS UK study #II

[usedtobeperkytina]

yes, the multiple systems involved points to CNS dysfunction or retrovirus.

Higher rate of lymphomas, as reported by Peterson, points to retrovirus. The reactivation of latent viruses points to retrovirus or CNS / immune system problem.

Tina

 

[Gerwyn]

SIV in primates. I've got tons of stuff relating to neurological dysfunction, no reason why all other boxes would not be ticked:

SIV model of neuroaids

http://www.scripps.edu/mind/fox/research.html



J Neurovirol. 2008 Aug;14(4):301-8.

Behavioral and neurophysiological hallmarks of simian immunodeficiency virus infection in macaque monkeys.

Cheney PD, Riazi M, Marcario JM.Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160-7185, USA. pcheney@kumc.edu
Macaque monkeys infected with various neurovirulent forms of simian immunodeficiency virus (SIV) represent highly effective models, not only of systemic acquired immunodeficiency virus (AIDS), but also neuroAIDS. Behavioral studies with this model have clearly established that SIV-infected monkeys show both cognitive and motor impairments resembling those that have been reported in human immunodeficiency virus (HIV)-infected humans. This paper combines data from a number of behavioral studies in SIV-infected macaque monkeys to obtain an overall estimate of the frequency of impairments in various motor and cognitive domains. The results were then compared to similar data from studies of HIV-infected humans. Whereas cognitive functions are most commonly impaired in HIV-infected humans, motor function is the domain most commonly impaired in SIV-infected monkeys. Electrophysiological studies in SIV-infected macaques have revealed deficits in motor-, somatosensory-, visual-, and auditory-evoked potentials that also resemble abnormalities in human HIV infection. Abnormalities in motor-evoked potentials were among the most common evoked potential deficits observed. Although differences in behavioral profiles of human HIV disease and SIV disease in monkeys exist, the results, nevertheless, provide strong validation for the use of macaque models for translational studies of the virology, immunology, pathophysiology, and treatment of neuroAIDS.PMID: 18780231

....Significant correlations were found between impaired performance on the bimanual motor test and axonal damage (accumulation of beta-amyloid precursor protein in the corpus callosum) as well as increased microglial activation and macrophage infiltration (levels of CD68 and Ham56 immunostaining). These results suggest that axonal damage is related to the behavioral impairment induced by infection with SIV. The axonal damage may result from neuroimmune responses, including microglial and macrophage activation. Therefore, axonal damage may be a morphologic manifestation of neuronal dysfunction that underlies development of behavioral impairment in HIV/SIV CNS infection. PMID: 12907390

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


Gerwyn you'll love this one:

... STUDY DESIGN/METHODS: Cognitive and motor function was assessed in rhesus macaque monkeys infected with simian immunodeficiency virus (SIV). In situ hybridization, immunohistochemistry, and quantitative image analysis were employed to assess the relations among productive infection, NO synthase (iNOS), and dendritic injury. RESULTS: Productive infection of cells of the macrophage lineage in CNS is associated with inflammation, increased expression of iNOS, and dendritic injury. The tests of cognitive and motor function employed were abnormal in both animals that had evidence of productive infection and those that did not. CONCLUSIONS: Increased NO accompanying productive infection and encephalitis may be one cause of neuronal injury in lentivirus infections of the CNS. Extension of tests of cognitive and motor function to late-stage AIDS in rhesus monkeys is needed to assess the potential role of NO-induced dendritic damage in lentiviral encephalopathy/AIDS dementia complex. PMID: 10413365

your ability to find relevant studies is quite amazing

 

[Gemini]

any way to bring these studies/findings to the attention of the Emory Univ XMRV macaque researchers?

 

[dannybex]

[The bad news is that I was contacted by a professional in the field who is very worried about XMRV right now and is not getting answers to his/her questions to the WPI. (Emails are not getting answered). This person outlined a scenario of contamination either at the Cleveland Clinic or the WPI. The contaminant is not an endogenous retrovirus but XMRV itself permeating all the samples.( I don't know how it doesn't get into the healthy controls). They were also worried about the efficacy of nested PCR - maybe someone can comment on that. They're also worried about the original cohort - specifically they're worried that the patients in it were selected on the basis of their positivity to another virus or for having T-cell rearrangements. Dr. Mikovits is not saying.

So they've asked repeated questions, and aren't getting any answers? Doesn't anyone else find this somewhat alarming?

 

[ukxmrv]

I've had replies for my questions. Plus a researcher I have been talking to has had answers to his questions (seen the emails) so I assumed that this was an isolated problem or a mistake

There is going to be a limit to what WPI can answer and how quickly.

I wonder what their questions were. Dr Mikovits has been "saying" to other people so why not this one - is the problem a real one, a mistake or "hearsay"?

 

[natasa778]

at least one of those 3 (?) questions has been answered by Judy M before, publicly, so don't see why she would be wasting time repeating the same thing... don't know about other two...

 

[dannybex]

I've had replies for my questions. Plus a researcher I have been talking to has had answers to his questions (seen the emails) so I assumed that this was an isolated problem or a mistake

There is going to be a limit to what WPI can answer and how quickly.

I wonder what their questions were. Dr Mikovits has been "saying" to other people so why not this one - is the problem a real one or "hearsay".

Perhaps 'alarming' was too strong of a word...but it's puzzling to say the least.

This came from Cort, so I woudn't call it hearsay. I know she's probasbly swamped with emails/calls...not to mention a ton of work, so hopefully this person/persons will get their answers soon.

d.

 

[ukxmrv]

D

The person may be misleading Cort or not telling the whole story. We simply do niot know. That's why I said "Hearsay" - not on Cort but on the person reporting this to him. Could be all sorts of things. Maybe they have a history, met before and hate one another or WPI is sick spending too much time on one person. I've seen people make similar complaints and then discovered the whole story afterwards. Now I don't tend to spend too much time on these fior that reason.

 

[free at last]

More should be discussed about the known uk positives

I know its been mentioned a few times about the small group of known uk positive CFS ME sufferes, But first it always seems to be talked about like hearsay or guessing, can anyone with utmost certainty say there has been 20 so far ( i saw this figure here ) tested positive in the uk.

Because if thats fact, one thing seems certain, unless this group that privately paid for the testing ( 50% of Sufferes tested was quoted positive ) is somehow a very select group completely outside this new uk failed study cohort ( seems a bit unlikely especially at 50% positve rates ) then 1 xmrv is in the UK FACT. 2 CFS ME patients are indeed much more heavily infected than healthy controls in the UK FACT. 3 why oh why is the new uk study with DR kerr onboard completly at odds with this figure ? Either somethings wrong with the WPI testing, or somethings wrong with the new UK study, be it either cohort ( think thats a bit unlikely ) or testing failings ? ( possibly both ? ) My moneys on the WPI, cant help but trust DR j. Seems so confident. I really think she cares about this issue and the patients themselves, Not saying others dont, But its a gut reaction thing. Im sure shes fighting for us like no other has before, ( except a select few and we know who they are ) The new uk study by the WPI will shed more light on these questions for sure, if the 50% figure holds up with a much larger group, Then what, what will the uk goverment and all the specialists in this country make of such a finding ? Seems unlikely that the WPI will find nothing, if they have already found 20 out of 40 UK CFS ME patients are infected,

Can anyone with utmost certainty confirm this figure, as from where i sit at the moment it offers real hope that XMRV maybe the cause or part of the cause of the illness. And refutes the 2 failed uk studys, by the sheer 50% positive rates being detected in this country,

One last thing why is Dr Kerr not interested in these points im making, Wouldnt he be ? shouldnt he be ? If i was him i would want to lnow why these results are at odds with a study with hes name in it ? Still waithing myself here for info when to give a sample for the new WPI uk study. I will certainly tell this group my result when i get it, have no idea when that could be though.

 

[Gerwyn]

Perhaps 'alarming' was too strong of a word...but it's puzzling to say the least.

This came from Cort, so I woudn't call it hearsay. I know she's probasbly swamped with emails/calls...not to mention a ton of work, so hopefully this person/persons will get their answers soon.

d.

anything from a third party source is heresay

 

[Gerwyn]

Why are you calling it a "disorder"? Isn't that Reeves used to say... "CFS is not a disease, it's a disorder." I call it a disease. One pathogen explaining ME/CFS would not be surprising one bit, evidence has been building for 25 years that (a) virus(es) are involved.

infuenza ebolla mad cow multiple sclerosis parkinsons encephalopathy mitochondrial dysfunction you can cause neuroimmunoendocrine symptoms by deleting three base sequences in mitochondrial dna