further transcripts, bits relevant to autism

[Guest guest]

.... Part 3, 20:00 min à 30:00 minCheney: If it were, weÕd see a lot more than 10 million Americans infected with it, so there must be something thatÕs inhibiting the effective transmission of that agent given those numbers. Ten million versus letÕs say one million. And also many people infected simply donÕt get sick. At least they donÕt get sick with CFS.IÕd like to turn next to that which I thought was a very interesting and very broad question, Judy, having to do with what is it about the biology and the pathophysiology of a retrovirus - letÕs say it that way rather than XMRV itÕs self à what is it about the biology and the pathophysiology of a retrovirus that fits with the syndrome of CFS? What is it that overlaps what we know about CFS and the possibility that a retrovirus might actually be causing this illness? Is there something about XMRV or a retrovirus in general, that fit with what weÕre seeing? And IÕve made a sort of a list of things and maybe IÕll just go through them, Judy, and see if you either agree or disagree and want to add to it?Number one: We found evidence of elevated RNase L activity in the Lake Tahoe epidemic of CFS way back in 1985. RNase L activity suggests the presence of a viral infection.Judy: ThatÕs correct. It canÕt do itÕs job and it can do a lot of bad things and overactive RNaseL will cause the cell to die and apoptos and fit itÕs self mediator ? into the blood stream.Cheney: The very presence of RNase L suggests viral etiology for that epidemic.Judy: ThatÕs correct.Cheney: NK function seems to define the illness. The very first paper on this was out of Japan back in 1987 describing what they said was low NK Syndrome which is CFS back in Japan. And low NK syndrome has been a feature of this disease. Do you think basically, XMRV can cause low NK function?Judy: Absolutely. A Natural Killer cellÕs job is to clear viral infected cells and to clear tumor cells. So if you have a retrovirus present which unchecked, itÕs continually expressed, and the NK cell canÕt clear it, it [NK cell] eventually becomes exhausted and of course, the virus can do something to the NK cell to allow it to persist. So cells whose job it is to kill virus infected cells canÕt kill XMRV or canÕt clear it, would then have defective NK cells, a persistent marker of infection.Cheney: In the Lake Tahoe epidemic many years ago, but also here in my clinic in Ashville, we frequently see an elevated CD4 to CD8 ratio, primarily due to CD8 depletion, and I wonder if you might comment. Is CD8 depletion something that XMRV might be able to cause?Judy: We donÕt see XMRV as a cytotoxic virus, thus far. Certainly, it is possible through indirect effects, through mediators or whatÕs known as cytokines, we could see dysregulation of the adaptive immune response which is the CD8 cell. But we donÕt see direct cytopathic. More this virus seems to be like HTLV-1 and not kill itÕs cells like HIV.Cheney: The CFS is highly associated with activation of herpes group viruses, especially EBV, HHV-6 and CMV. I was wondering if XMRV infection is consistent with the activation of other human herpes viruses that they are already infected with.Judy: Yes, because XMRV, the hypothesis is that the virus creates an underlying immune deficiency, because as you just said, the NK and maybe the CD8 cells donÕt work so youÕve got an underlying immune deficiency, so if your immune system canÕt do itÕs job, so that viruses that you harbor in your body like EBV and CMV which are near ubiquitous around the world, are not able to be controlled by an immune system that is not functioning up to par and actually immune deficient so, the hypothesis is, just like HIV/AIDS, it creates an underlying immune deficiency. So, as you know, CMV retinitis is an AIDS defining illness, as is chronic EBV and EBV malignancy. So it makes perfect sense how a retrovirus can cause an underlying immune deficiency. Essentially, we see what we see in this disease, not only herpes viruses but things like chronic lyme, which are also found in CFS cohorts.Cheney: ThereÕs a lot of brain involvement in CFS and it comes in the form of neuro-cognitive complaints; it comes in the form of neuro-behavioral shifts; it comes in the form of abnormal MRI scans that are typically non-specific but abnormal; it comes in the form of subtle neurological findings on exams such as hyper-reflexia and disturbances of the vestibular apparatus. So my question is, do you think XMRV could be causing neurological problems like this?Judy: Oh absolutely, and again we go back to other retroviruses, HTLV-1, in addition to leukemia that it is causative for, has associated with it a disease called HTVL-1 associated myelopathy, where it is a myelopathy type disease. The patients stagger, canÕt walk, end up in wheelchairs, and it is related directly to viral load but they donÕt understand all of the mechanisms. Importantly, in XMRV family members and animals??, the envelope protein actually is a neurotoxin, so parts of the viruses by themselves, without all the infectious replicating virus, can cause neurotoxicity. We are actually investigating the envelope protein of this virus as potentially a neurotoxin.Cheney: A lot of these patients, if you investigate their immune system, thereÕs evidence of significant activation of the immune system of almost any parameter that you look at, particularly cytokine elevations of various kinds and evidence of TGF beta 1 activations. Suggesting the immune system is really activated and thereÕs kind of a counter response trying to tone it down. Is immune activation, which we almost see universally by cytokine markers consistent with XMRV infection?Judy: Well yes, and every other retroviral infection absolutely, Again, it goes unchecked, so the immune system is trying to do itÕs job, clear the virus, keep the virus down, and when the virus goes unchecked, it causes the kind of things we discussed with elevated T cells is the problem. So in the face of chronic inflammation you develop immune deficiency.Cheney: And this is sort of a cross-over from the biology and pathophysiology to infectiousness issue. We see CFS occurring n clusters. WeÕve seen cluster formations for 25 years. We were involved in a cluster in Lake Tahoe; a cluster in Yearington; a cluster in Placerville; and Bell was in a cluster in Lyndonville, NY. We see clusters in school systems. We see clusters in families. We see clusters in airline attendants. This is interesting. Is it possible that these clusters could be driven by a retrovirus?Judy: Absolutely. ItÕs highly possible and we are actively investigating it