David Kirby on HuffPo: Is Autism Associated with a Viral Infection?
Click HERE to comment at HuffPo please.
...Researchers tested blood samples from a "small group of children" with autism and found that 40% of them were positive for XMRV, according to a statement from the Nevada Commission on Autism Spectrum Disorders. More testing is underway which, the Commission said, "could dramatically increase that 40% positive finding." (Given the small sample size, such a statement is purely speculative).
As Dr. Mikovits explained to a television news program in Nevada, "It is not in the paper and not reported, but we have actually done some of these studies (in ASD children) and found the virus in a significant number of samples that we have tested for. It could be linked to a number of neuro-immune diseases, including autism. It certainly won't be all, because there are genetic defects that result in autism. But there are also the environmental effects; there is always the hypothesis that, 'My child was fine and then they got sick, and then they got autism.'"
Now that the VIP lab in Reno, Nevada has agreed to do testing and put forth a price list, how do we know which mxrv test to do? And, are we looking for dormant, active, anti-bodies? The tests are out of pocket so we need to make sure to do the right one; how do we find out?
Posted by: A. F. | October 24, 2009 at 02:46 PM
so are some vaccines cultured on any kind of mouse ingredient? Wouldn't surprise me...
Posted by: jen | October 14, 2009 at 12:15 PM
HAve anyone really questioned the health of older autistics as I have? I went to Dr Walsh and he said AUTISM IS NEURODEGNERATIVE..unlike what the DAN doctors are telling you. He sees autistics in their twenties and thirties, too much onsets of schizophrenia, dementia, cancers, heart attacks, worsening of seizures...if you want to ask where they are, they might jist be in the grave (in heaven). If you give no antioxidants, the brain deteriorates. That's where the autistics are. And, they also have gut problems.
Posted by: Kathy Blanco | October 14, 2009 at 11:42 AM
From "across the pond":-
So, if "a virus" can cause autism then what's to prevent one or more of the Measles, Mumps and Rubella viruses causing autism? Is this a back door into an eventual admission that the MMR vaccine can cause autism in, say, a susceptible sub-set?
Posted by: ElizaCassandra | October 14, 2009 at 03:20 AM
KDM, great point about the SV40 virus that was in polio vaccines -- especially since XMRV "is blood-borne, and not transmitted through the air."
Posted by: CM | October 13, 2009 at 09:02 PM
Such wonderful information here and certainly it is good to understand the infections that autistic individuals are prone to.
Gatogorra, thankyou for your logical , incisive comments.
One has to wonder if this virus , while perhaps real , is also a fake rabbit for the autism greyhounds to chase- one more piece of the divert and delay tactics which are very important for those who have their backs to the wall for their criminal negligence in allowing toxic materials into vaccines in quantities far above EPA "safe levels"
Now that the "Autism is genetic" card is wearing out, "Autism is caused by a virus" is quite a terrific idea. No wonder Dr. Snyderman states that viruses can cause OCD . Autism is just one small step further. AOA friends- We should have predicted this one.
Hmm... I wonder if autistic kids in other countries such as India, China, Korea have this same virus ? My guess is that they do not
Posted by: Cherry Sperlin Misra | October 13, 2009 at 02:26 PM
Just wanted to say;
It is so nice to be within the folds of so many people that state their case with such passion. You always say exactly what is on my mind, but so much better!
Posted by: Benedetta | October 13, 2009 at 12:21 PM
If there is a virus, that wouldn't surprise me.. I've wondered if my son has a chronic blood infection due to a virus or mycoplasma that causes flare ups of inflammation and swelling in the brain. It would help if they would simply do a viral or mycoplasma screening as part of the of the diagnosing. This could change the whole treatment course.
Posted by: Sarah | October 13, 2009 at 11:07 AM
We are making this too hard.
Strep will set up inflammation in the blood vessels. I went to a funeral 40 years ago of a young woman that died of heart disease brought on by an autoimmune response from strep when she was young.
Strep also is the known culprit to some OCB too.
Vasculitis is not a new diseae. I am sure that many pathogens can set up an autoimmune response of inflammation in the blood vessels
Not only pathgens but vaccines; both antigens and adjuvents.
Men for years and years and years get more heart attacks than women (this is also the same vascular inflammation that is showing up in our children) Medical research - did they ever figure out why more men than women?
The first DPT shot my son had - on his next office visit they discovered a heart murmur.
The second DPT shot he passed out
The third DPT shot he had a stroke.
So now we have the population getting vasculitis not only from pathogens but vaccines, both antigens and adjuvents.
This whole thing made my brain hurt.
Posted by: Benedetta | October 13, 2009 at 10:54 AM
From NY TImes .... 10/12 ...
Could a virus be the cause of chronic fatigue syndrome?
A study published last week in the journal Science suggested that might be the case, reporting that many patients who had the syndrome were infected with a recently discovered virus.
Chronic fatigue syndrome has long been a medical mystery and the subject of debate, sometimes bitter, among doctors, researchers and patients. It affects at least one million Americans, causing extreme fatigue, muscle and joint pain, sleep problems, difficulty concentrating and other symptoms. Its cause is unknown, symptoms can last for years and there is no effective treatment. Researchers disagree about whether it is one disease or a collection of symptoms that may have different causes in different patients. It has sometimes been stigmatized as more mental than physical, with patients labeled neurotic, depressed or hypochondriacal. Many patients find even the name of the disorder offensive, a not-so-subtle hint that it is not a real disease.
The new report has intrigued scientists, been seen as vindication by some patients and inspired hope for a treatment.
“I just feel like the whole future has changed for us,” said Anne Ursu, 36, a writer living in Cleveland who has had the syndrome in the past.
But the new study is not conclusive, and a great deal of work remains to be done to find out whether the new virus really does play a role. Just detecting it in patients does not prove it is what made them sick; people with the syndrome may have some other underlying problem that makes them susceptible to the virus, which could be just a passenger in their cells.
Even so, thousands of patients have already contacted scientists, asking to be tested, said Dr. Judy Mikovits, the first author of the study and the research director at the Whittemore Peterson Institute in Reno, a research center created by the parents of a woman who has the syndrome. Dr. Mikovits said she expected a test to become available “within weeks.”
The new suspect is a xenotropic murine leukemia virus-related virus, or XMRV, which probably descended from a group of viruses that cause cancer in mice. How or when XMRV found its way into humans is unknown. But it has also been linked to cancer in people: it was first identified three years ago, in prostate cancer, and later detected in about one-quarter of biopsies from men with that disease (and in only 6 percent of benign biopsies). It is a retrovirus, from the same notorious family that causes AIDS and leukemia in people. .......
Posted by: Diane | October 13, 2009 at 10:44 AM
Gatogorra, not sure which one you had in mind, there are several
Disintegration of retroviruses by chelating agents - V. Wunderlich1 and G. Sydow1(1) April 1982. Central Institute for Cancer Research, Robert-Rössle-Institute, Academy of Sciences of the German Democratic Republic
Metal chelators as potential antiviral agents. Hutchinson DW. Antiviral Res. 1985 Aug;5(4):193-205 Klin Wochenschr. 1991 Oct 2;69(15):722-4.
Inhibition of Tat-mediated HIV-1-LTR transactivation and virus replication by sulfhydryl compounds with chelating properties - DEMIRHAN Ilhan et al. Anticancer Res. 2000 Jul-Aug;20(4):2513-7
Advances in two-metal chelation inhibitors of HIV integrase Authors: Johns, Brian A; Svolto, Angilique C Source: Expert Opinion on Therapeutic Patents, Volume 18, Number 11, November 2008 , pp. 1225-1237(13)
Inhibition of human immunodeficiency virus type 1 replication in human mononuclear blood cells by the iron chelators deferoxamine, deferiprone, and bleomycin. Georgiou NA et al J Infect Dis. 2000 Feb;181(2):484-90.
several more listed on http://autismcalciumchannelopathy.com/HIV_and_Autism.html
(sorry links lost, you will have to google or go to pubmed for papers - if any in particular I have most abstracts and some full versions, let me know which one)
and several chelators patented as antiRetroviral agents, with lots of info on patent website.
Posted by: Natasa | October 13, 2009 at 10:05 AM
@mother, that is interesting re DPVIV enzyme. Clostridia does the same, at least in culture.
Now have a look at these (sorry links not working, try googling them for full versions or abstracts)
Early impairment of gut mucosal immunity in HIV-1-infected children. Quesnel A et al Clin Exp Immunol. 1994 Sep;97(3):380-5.
Poliovirus vaccine strains detected in stool specimens of immunodeficient children in South Africa. Pavlov DN Diagn Microbiol Infect Dis. 2006 Jan;54(1):23-30. Epub 2005 Nov 14.
Enteric pathogens associated with gastrointestinal dysfunction in children with HIV infection. Ramos-Soriano AG et al Mol Cell Probes. 1996 Apr;10(2):67-73.
Gastrointestinal dysfunction and disaccharide intolerance in children infected with human immunodeficiency virus. Yolken RH et al J Pediatr. 1991 Mar;118(3):359-63.
Intestinal malabsorption of HIV-infected children: relationship to diarrhoea, failure to thrive, enteric micro-organisms and immune impairment. The Italian Paediatric Intestinal/HIV Study Group. AIDS. 1993 Nov;7(11):1435-40.
Intestinal permeability in patients infected with the human immunodeficiency virus. Tepper RE Am J Gastroenterol. 1994 Jun;89(6):878-82.Efficacy of oral pancreatic enzyme therapy for the treatment of fat malabsorption in HIV-infected patients. Carroccio A et al Aliment Pharmacol Ther. 2001 Oct;15(10):1619-25.
The effect of antenatal vitamin A and beta-carotene supplementation on gut integrity of infants of HIV-infected South African women. Filteau S et al J Pediatr Gastroenterol Nutr. 2001 Apr;32(4):464-70.
uncanny or what?
Posted by: Natasa | October 13, 2009 at 10:01 AM
Causation or correlation? Maybe it's just easier with vaccine damage to GET this particular virus.
I'm so tired of the continual contortions the medical establishment goes through to avoid looking at the elephant in the room.
Where was this virus 100 years ago? Did it just appear? Where are the legions of autistic, diaper wearing, head banging 60 year olds? Did children not bring viruses home from school and give them to infant siblings?
I find it similarly interesting that HIV has supposedly been around for a very long time but it's only in the span of time we've been massively vaccinating the population of Africa that it became pandemic...
Posted by: HFAmomto3HFAgirls | October 13, 2009 at 09:54 AM
HIV inhibit the enzyme CD26/DPPIV, and if XMRV do the same, that might explain why autists react to gluten and casein whithout allergy. The CD26/DPPIV is essential to digest prolin-rich proteins, and with DPPIV inhibited, the proteins will end up as casomorphins and glutenmorphins (opioids).
It´s said that that this viral infection do not explain all the symptomes in CFS, but add the burden of opioids from food, and the picture is clearer.
Posted by: mother | October 13, 2009 at 08:54 AM
This is some amazing shit.
Posted by: Charlie | October 13, 2009 at 08:09 AM
Why more boys? A virus maybe the set up but something is happening to mostly boys. Mercury seems to fit that bill as the final push.
I think we should look at the cell cultures. How else would a mouse virus jump to humans.
Posted by: Maggie | October 13, 2009 at 06:18 AM
Many modalities currently used for treating autism have proven or suspected antiretroviral effects:
• chelation of metals inhibits HIV virus integration into human DNA. Retroviruses in general are desintegrated by chelation agents in vitro. Several chelators have been patented as antiretroviral agents. Several agents with chelating properties, such as alpha lipoic acid (ALA) and NAC have been shown to reduce viral load in HIV positive individuals
• Tetracycline antibiotics (one currently on trial for autism) inhibit HIV in vitro through same mechanism as chelation agents.
• HIV is inhibited by glutathione and agents that raise glutathione
• Acyclovir/valacyclovir (antiviral agent with anti-herpevirus activity, with anecdotal reports of amelioration of autistic symptoms) has been shown to reduce HIV viral load in HIV positive individuals. The mechanisms are not clear.
• Hyperbaric oxygen has been shown to inhibit HIV and reduce viral load.
• Pancreative enzymes trial showed beneficial effect in HIV positive.
• Methylation agents such as cobalamins and SAMe directly inhibit HIV activity and maintain its latency.
Posted by: Natasa | October 13, 2009 at 02:42 AM
Another VERY interesting thing about RnaseL: CFS people with high low molecular weight (fragmented) RnaseL have been found to have a hightened sensitivity to MERCURY
Posted by: Natasa | October 13, 2009 at 02:41 AM
Maria, Redlabs http://www.redlabsusa.com/ is testing RnaseL. Its fragmentation is INDUCED by a chronic viral infection... which would lead to a theory of a dual hit - ie one pathogen induces deficiency, another has a free reign and easily gains permanent upper hand over cellular machinery.
Redlabs currently running a small study on viruses in autism (not sure if they are looking into RnaseL). Worth phoning them to find out if still taking participants
Posted by: Natasa | October 13, 2009 at 02:40 AM
Donna Alvado - there is some information on this CFS forum on how to get tested for XMRV. http://forums.aboutmecfs.org/forumdisplay.php?f=54 You might have to wait 6 months. I would also check the Whittemore Peterson Institute website, they will have the best information. http://www.wpinstitute.org/xmrv/index.html
There may also be information on prohealth, but I'm not registered there, so I can't read it.
julie - you asked "How prevalent is this virus in the general population?"
4% of controls.
Posted by: Beta | October 13, 2009 at 02:35 AM
So, vaccines are safe for the whole population except if your body has the wrong kind of micro flora, or a sure enough pathogen?
Well, then problem solved.
Strep and OCB has been know about for a least 30 years, and had us very watchful. Better get that antibiotic, and soon, (which doctors so begrudingly give), esp now a days. They brag about it too. OHHH, patient has to be close to death and really sick before I give it to 'em.
Strep is one of those things if it goes on too long will set up an autoimmune response in the blood vessels and can affect the brain and/or heart. Sort of like--- what the whooping cough vaccine does.
Strep - act of chance.
Vaccine not an act of chance and somebody said it was just super safe.
Posted by: Benedetta | October 13, 2009 at 12:15 AM
Biomed Pharmacother. 1998;52(9):386-90. Links
The 2-5A system in viral infection and apoptosis.Castelli J, Wood KA, Youle RJ.
Biochemistry Section, NINDS, NIH, Bethesda, MD 20892, USA.
The 2-5A system is an established endogenous antiviral pathway. Interferon treatment of cells leads to an increase in basal, but latent, levels of 2-5A-dependent RNase (RNase L) and the family of 2'-5' oligoadenylate synthetases (OAS). Double-stranded RNA, thought to be derived from viral replication intermediates, activates OAS. Activated OAS converts ATP into unusual short 2'-5' linked oligoadenylates called 2-5A [ppp5'(A2'p5')2A]. The 2-5A binds to and activates RNase L which cleaves single stranded RNA with moderate specificity for sites 3' of UpUp and UpAp sequences, and thus leads to degradation of cellular rRNA. During apoptosis, generalized cellular RNA degradation, distinct from the differential expression of mRNA species that may regulate specific gene expression during apoptosis, has been observed. The mechanism of RNA breakdown during apoptosis has been commonly considered a non-specific event that reflects the generalized shut down of translation and homeostatic regulation during cell death. Due to the similar RNA degradation that occurs during both apoptosis and viral infection we investigated the potential role of RNase L in apoptosis. To investigate whether RNase L activity could lead to apoptosis, NIH3T3 cells were transfected with a lac-inducible vector containing the human RNase L gene. Treatment of these cells with isopropylthiogalactoside (IPTG) caused loss of cell viability that was confirmed as an apoptotic cell death by morphological and biochemical criteria. Similarly, specific allosteric activation of endogenous RNase L by introduction of 2-5A directly into L929 cells also induced apoptosis. In L929 cells poly(I).poly(C) treatment in combination with interferon caused an increase in apoptosis whereas neither interferon or double stranded RNA alone altered cell viability. Therefore, increased expression or activation of RNase L causes apoptosis. Inhibition of RNase L, specifically with a dominant negative mutant, suppressed poly(I)Ypoly(C)-induced apoptosis in interferon-primed fibroblasts. Poliovirus, a picornovirus with a single-stranded RNA genome, causes apoptosis of HeLa cells. Expression of the dominant negative inhibitor of RNase L in HeLa prevented virus-induced apoptosis and maintained cell viability. Thus, reduction or inhibition of RNase L activity prevents apoptosis. Both apoptosis and the 2-5A system can provide defense against viral infection in multicellular organisms by preventing production and therefore spread of progeny virus. RNase L appears to function in both mechanisms, therefore, initiation of apoptosis may be one mechanism for the antiviral activity of the 2-5A system.
RNA. 2008 Jun;14(6):1026-36. Epub 2008 Apr 21. Links
A viral RNA competitively inhibits the antiviral endoribonuclease domain of RNase L.Townsend HL, Jha BK, Han JQ, Maluf NK, Silverman RH, Barton DJ.
Department of Microbiology, University of Colorado Denver, School of Medicine, Aurora, Colorado 80045, USA.
Ribonuclease L (RNase L) is a latent endoribonuclease in an evolutionarily ancient interferon-regulated dsRNA-activated antiviral pathway. 2'-5' oligoadenylate (2-5A), the product of dsRNA-activated oligoadenylate synthetases (OASes), binds to ankyrin repeats near the amino terminus of RNase L, initiating a series of conformational changes that result in the activation of the endoribonuclease. A phylogenetically conserved RNA structure within group C enteroviruses inhibits the endoribonuclease activity of RNase L. In this study we report the mechanism by which group C enterovirus RNA inhibits RNase L. Viral RNA did not affect 2-5A binding to RNase L. Rather, the viral RNA inhibited the endoribonuclease domain. We used purified RNase L, purified 2-5A, and an RNA substrate with a 5' fluorophore and 3' quencher in FRET assays to measure inhibition of RNase L activity by the viral RNA. The group C enterovirus RNA was a competitive inhibitor of the endoribonuclease with a K(i) of 34 nM. Consistent with the kinetic profile of a competitive inhibitor, the viral RNA inhibited the constitutively active endoribonuclease domain of RNase L. We call this viral RNA the RNase L competitive inhibitor RNA (RNase L ciRNA).
A scientific journey through the 2-5A/RNase L system.
Posted by: María Luján | October 12, 2009 at 11:38 PM
J Immunol. 2007 Nov 1;179(9):5728-37. Links
Differential regulation of the nature and functions of dendritic cells and macrophages by cathepsin E.Kakehashi H, Nishioku T, Tsukuba T, Kadowaki T, Nakamura S, Yamamoto K.
Department of Pharmacology, Graduate School of Dental Science, Kyushu University, Fukuoka, Japan.
The aspartic proteinase cathepsin E is localized mainly in the endosomal structures of APCs and has been implicated in a variety of immune responses, however, the precise roles of cathepsin E in these cells remain speculative. In this study, we report the effect of disrupting the gene encoding cathepsin E on the nature and functions of dendritic cells (DCs) and macrophages derived from mouse bone marrow precursors, as well as mouse peritoneal macrophages. Whereas cathepsin E deficiency induced the accumulation of the lysosome-associated membrane protein (LAMP)-1 and LAMP-2 and elevated the lysosomal pH in macrophages, it did not have these effects on DCs. Although cathepsin E deficiency also caused a marked decrease in degradation of phagocytosed OVA and chemotactic responses to MCP-1 and fMLP by macrophages, these abilities were little affected in DCs by the absence of cathepsin E. Interestingly, cathepsin E deficiency markedly decreased the ability of macrophages to present intact OVA, as well as an OVA-derived antigenic peptide (266-281), to cognate T cells, while that of DCs was inversely enhanced by the absence of this protein. This paradox was resolved, in part, by the enhanced phagocytic activity and the increased expression of the costimulatory molecules CD86, CD80, and CD40, which amplify the response of T cells, in cathepsin E-deficient DCs compared with the wild-type cells.
These results indicate that cathepsin E differentially regulates the nature and function of DCs and macrophages
Posted by: María Luján | October 12, 2009 at 11:23 PM
Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1655-60.
An infectious retrovirus susceptible to an IFN antiviral pathway from human prostate tumors.Dong B, Kim S, Hong S, Das Gupta J, Malathi K, Klein EA, Ganem D, Derisi JL, Chow SA, Silverman RH.
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
We recently reported identification of a previously undescribed gammaretrovirus genome, xenotropic murine leukemia virus-related virus (XMRV), in prostate cancer tissue from patients homozygous for a reduced activity variant of the antiviral enzyme RNase L. Here we constructed a full-length XMRV genome from prostate tissue RNA and showed that the molecular viral clone is replication-competent. XMRV replication in the prostate cancer cell line DU145 was sensitive to inhibition by IFN-beta. However, LNCaP prostate cancer cells, which are deficient in JAK1 and RNase L, were resistant to the effects of IFN-beta against XMRV. Furthermore, DU145 cells rendered deficient in RNase L with siRNA were partially resistant to IFN inhibition of XMRV. Expression in hamster cells of the xenotropic and polytropic retrovirus receptor 1 allowed these cells to be infected by XMRV. XMRV provirus integration sites were mapped in DNA isolated from human prostate tumor tissue to genes for two transcription factors (NFATc3 and CREB5) and to a gene encoding a suppressor of androgen receptor transactivation (APPBP2/PAT1/ARA67).
Our studies demonstrate that XMRV is a virus that has infected humans and is susceptible to inhibition by IFN and its downstream effector, RNase L.
What is the role of RNase L??
Biochimie. 2007 Jun-Jul;89(6-7):789-98. Epub 2007 Feb 20. Diverse functions of RNase L and implications in pathology.Bisbal C, Silverman RH.
IGH UPR CNRS 1142, 141 rue de la Cardonille, 34396 Montpellier, France.
The endoribonuclease L (RNase L) is the effector of the 2-5A system, a major enzymatic pathway involved in the molecular mechanism of interferons (IFNs). RNase L is a very unusual nuclease with a complex mechanism of regulation. It is a latent enzyme, expressed in nearly every mammalian cell type. Its activation requires its binding to a small oligonucleotide, 2-5A. 2-5A is a series of unique 5'-triphosphorylated oligoadenylates with 2'-5' phosphodiester bonds. By regulating viral and cellular RNA expression, RNase L plays an important role in the antiviral and antiproliferative activities of IFN and contributes to innate immunity and cell metabolism. The 2-5A/RNase L pathway is implicated in mediating apoptosis in response to viral infections and to several types of external stimuli. Several recent studies have suggested that RNase L could have a role in cancer biology and evidence of a tumor suppressor function of RNase L has emerged from studies on the genetics of hereditary prostate cancer.
Med Sci (Paris). 2008 Oct;24(10):859-64.
[RNase L, a crucial mediator of innate immunity and other cell functions
Bisbal C, Salehzada T.
Inserm ERI25-EA 4202, Muscle et Pathologies, Bâtiment Crastes de Paulet, CHU Arnaud de Villeneuve, 371, avenue du Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France.
The 2-5A/RNase L pathway is one of the first cellular defences against viruses. RNase L is an unusual endoribonuclease which activity is strictly regulated by its binding to a small oligonucleotide, 2-5A. 2-5A itself is very unusual, consisting of a series of 5'- triphosphorylated oligoadenylates with 2'-5' bonds. But RNase L activity is not limited to viral RNA cleavage. RNase L plays a central role in innate immunity, apoptosis, cell growth and differentiation by regulating cellular RNA stability and expression. Default in its activity leads to increased susceptibility to virus infections and to tumor development. RNase L gene has been identified as HPC1 (Hereditary Prostate Cancer 1) gene. Study of RNase L variant R462Q in etiology of prostate cancer has led to the identification of the novel human retrovirus closely related to xenotropic murine leukemia viruses (MuLVs) and named XMRV.
PLoS Pathog. 2009 Oct;5(10):e1000602. Epub 2009 Oct 2.
RNase L mediated protection from virus induced demyelination.Ireland DD, Stohlman SA, Hinton DR, Kapil P, Silverman RH, Atkinson RA, Bergmann CC.
Department of Neuroscience, Lerner Research Institute, The Cleveland Clinic, Cleveland, Ohio, United States of America.
IFN-alpha/beta plays a critical role in limiting viral spread, restricting viral tropism and protecting mice from neurotropic coronavirus infection. However, the IFN-alpha/beta dependent mechanisms underlying innate anti-viral functions within the CNS are poorly understood. The role of RNase L in viral encephalomyelitis was explored based on its functions in inhibiting translation, inducing apoptosis, and propagating the IFN-alpha/beta pathway through RNA degradation intermediates. Infection of RNase L deficient (RL(-/-)) mice with a sub-lethal, demyelinating mouse hepatitis virus variant revealed that the majority of mice succumbed to infection by day 12 p.i. However, RNase L deficiency did not affect overall control of infectious virus, or diminish IFN-alpha/beta expression in the CNS. Furthermore, increased morbidity and mortality could not be attributed to altered proinflammatory signals or composition of cells infiltrating the CNS. The unique phenotype of infected RL(-/-) mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. Increased tissue damage coincided with sustained brain stem infection, foci of microglia infection in grey matter, and increased apoptotic cells. These data demonstrate a novel protective role for RNase L in viral induced CNS encephalomyelitis, which is not reflected in overall viral control or propagation of IFN-alpha/beta mediated signals. Protective function is rather associated with cell type specific and regional restriction of viral replication in grey matter and ameliorated neurodegeneration and demyelination.
Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20816-21. Epub 2008 Dec 15. Links
An essential role for the antiviral endoribonuclease, RNase-L, in antibacterial immunity.Li XL, Ezelle HJ, Kang TJ, Zhang L, Shirey KA, Harro J, Hasday JD, Mohapatra SK, Crasta OR, Vogel SN, Cross AS, Hassel BA.
Graduate Program in Molecular Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Type I IFNs were discovered as the primary antiviral cytokines and are now known to serve critical functions in host defense against bacterial pathogens. Accordingly, established mediators of IFN antiviral activity may mediate previously unrecognized antibacterial functions. RNase-L is the terminal component of an RNA decay pathway that is an important mediator of IFN-induced antiviral activity. Here, we identify a role for RNase-L in the host antibacterial response. RNase-L(-/-) mice exhibited a dramatic increase in mortality after challenge with Bacillus anthracis and Escherichia coli; this increased susceptibility was due to a compromised immune response resulting in increased bacterial load. Investigation of the mechanisms of RNase-L antibacterial activity indicated that RNase-L is required for the optimal induction of proinflammatory cytokines that play essential roles in host defense from bacterial pathogens. RNase-L also regulated the expression of the endolysosomal protease, cathepsin-E, and endosome-associated activities, that function to eliminate internalized bacteria and may contribute to RNase-L antimicrobial action. Our results reveal a unique role for RNase-L in the antibacterial response that is mediated through multiple mechanisms. As a regulator of fundamental components of the innate immune response, RNase-L represents a viable therapeutic target to augment host defense against diverse microbial pathogens.
In Vivo. 2008 Jan-Feb;22(1):115-21. Links
Unravelling intracellular immune dysfunctions in chronic fatigue syndrome: interactions between protein kinase R activity, RNase L cleavage and elastase activity, and their clinical relevance.Meeus M, Nijs J, McGregor N, Meeusen R, De Schutter G, Truijen S, Frémont M, Van Hoof E, De Meirleir K.
Department of Human Physiology, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Belgium.
This study examined possible interactions between immunological abnormalities and symptoms in CFS. Sixteen CFS patients filled in a battery of questionnaires, evaluating daily functioning, and underwent venous blood sampling, in order to analyse immunological abnormalities. Ribonuclease (RNase) L cleavage was associated with RNase L activity (rs=0.570; p=0.021), protein kinase R (PKR) (rs=0.716; p=0.002) and elastase activity (rs=0.500; p=0.049). RNase L activity was related to elastase (rs=0.547; p=0.028) and PKR activity (rs=0.625; p=0.010). RNase L activity (rs=0.535; p=0.033), elastase activity (rs=0.585; p=0.017) and RNase L cleavage (rs=0.521; p=0.038) correlated with daily functioning. This study suggests that in CFS patients an increase in elastase activity and subsequent RNase L cleavage is accompanied by increased activity of both the PKR and RNase L enzymes. RNase L and elastase activity are related to daily functioning, thus evidence supporting the clinical importance of these immune dysfunctions in CFS patients was provided.
Now the RNAse L (Ribonuclease L) has important roles in antimicrobian and antiviral functions and inhibites the XMRV virus
I wonder what is the status of the RNAse L in different subgroups of ASD...
Posted by: María Luján | October 12, 2009 at 11:18 PM
Posted by: Kathy Blanco | October 12, 2009 at 11:13 PM
I'm remembering Dr. Kent Holtorf saying recently on Fox News that he has seen people with chronic fatigue syndrome and fibromyalgia devastated by vaccines (AoA 9/26).
Posted by: Twyla | October 12, 2009 at 10:54 PM
Note that infectious pathogens are included among the possible biological stressors that can contribute to the onset of CFS. In particular, Borrelia burgdorferi, the bacterium responsible for Lyme disease, has been found to deplete glutathione in its host (96). This may explain the very similar pathophysiologies of chronic Lyme disease and CFS. This may also explain the epidemic clusters of CFS, which seem to have been produced by a virulent infectious pathogen (or pathogens). Perhaps the genetic factors are less important in producing the onset if a very virulent pathogen is present.
AH, so the perfect STORM SET UP, to not handle vaccines well...ya think?
Posted by: Kathy Blanco | October 12, 2009 at 09:26 PM
Another virus PASSED down from mother to child..(think of mom with CFS and has a child with autism.)
This virus from polio vaccines....
Posted by: Kathy Blanco | October 12, 2009 at 09:00 PM
Depletion of glutathione by Borrelia burgdorferi
1. Bb requires cysteine for its metabolism .
2. Cysteine diffuses passively into Bb from its host, i.e. there is no active transporter protein .
3. Bb uses cysteine in the synthesis of several of its essential enzymes: Osp A, Osp B, CoASH, a hemolysin, and others [2,3].
4. Bb does not use glutathione for its redox control. Instead, it uses reduced Coenzyme A (CoASH) .
5. Cysteine is the rate-limiting amino acid for the synthesis of glutathione in humans, so that depletion of cysteine will produce depletion of glutathione .
6. Bb lowers the cysteine and glutathione levels in its human host, and inhibits the activity of glutathione peroxidase .
7. Low glutathione and low activity of glutathione peroxidase allow a rise in hydrogen peroxide concentration and oxidative stress .
8. Elevation of hydrogen peroxide causes Bb to assume its cyst form , in which it is less vulnerable to antibiotics .
Posted by: Kathy Blanco | October 12, 2009 at 08:57 PM
oops, didn't post
Posted by: Kathy Blanco | October 12, 2009 at 08:55 PM
Please look at this article, note GLUTATHIONE BLOCk, Increased oxidative stress caused by BORRELIOSIS....(lyme)....
Posted by: Kathy Blanco | October 12, 2009 at 08:54 PM
Interestingly, both CFS and Autism have similar biomedical problems, aka, infections, mercury toxicity, metabolism problems, mitochondrial, glutathione block, etc....
Posted by: Kathy Blanco | October 12, 2009 at 08:49 PM
Natasa-- could you post the link about children with AIDS dementia receiving chelation therapy? The one in which researchers found the chelator was actually breaking up the virus? I think a lot of people would be interested in that information in light of this study.
Posted by: Gatogorra | October 12, 2009 at 08:24 PM
Thank you David. My head is spinning.
Like KDM, the first thing I thought of when I read that the virus is being investigated in diseases like CFS, autism and prostate cancer was "SV40"-- the cancer causing virus that was in a polio vaccine.
The second thing I thought of when I read the virus was "blood borne" is that the press is going to howl that all autism moms are sluts or intravenous drug users-- that the virus is an an STD.
Why wouldn't close to 100% of children (save for that tiny percentage with genetically "mediated" forms) with autism have this virus? I just don't believe in the "take-your-pick-could-be-anything" cause of autism. I think the cause(s) will be limited to one or two substances or set of related events that mimic each other. If this virus isn't in all children with autism, then they'll surely find that another-- perhaps a vaccine strain (maybe two or so in combination, administered at the same time)-- entirely mimics the effects and that the other remaining percentage of children are effected by that. And it could be that none of these viruses would be able to do so much damage without simultaneous mercury/metal toxicity.
Did they make any other observations about the subjects who were positive for the virus, such as...they were especially tired? Like maybe they had chronic fatigue on top of autism?
I'm wondering along with David if-- like Karposi's sarcoma and AIDS--children with autism are just especially prone to contract this. We all know that children with autism get thrush. But thrush-- while it seems to worsen symptoms of autism-- isn't the cause of autism. AIDS patients also get thrush-- not a cause there either.
"The finding that Hpc1 maps to the RNase L gene suggested that inherited defects in RNase L might allow for infection with an oncogenic virus, leading to PC [prostate cancer]"
So the idea is that a genetic variation makes some people more vulnerable to a cancer causing virus.
But what if a pharmaceutical product created an immune susceptibility which mimicked this genetic "vulnerability"? For instance, it was long believed that MELAS, or "Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke" was a genetic disease and that if pharmaceuticals had anything to do with it (people have suddenly developed the full syndrome while on neuroleptics, antidepressants or anticonvulsive drugs with hugely elevated frequency), it was because the drugs-- so industry scientists said-- brought out the latant gene expression of MELAS. But now some researchers are finding that the genetic condition itself can be entirely replicated by drugs-- meaning one does not have to have any "latant" or underlying genetic defect to develop MELAS. More and more, they're finding that pharmaceuticals can entirely mimic what were once solely genetic disorders-- with or without anything "genetic" underlying.
Posted by: Gatogorra | October 12, 2009 at 08:22 PM
This Virus-Autism connection may not be far fetched at all.
A couple of weeks ago the Today Show had a segment about a 9 year old typical boy who suddenly developed severe OCD behaviors. After more than a year of "tests" they said he was severely OCD and should be institutionalized. A few months later they discovered he actually had the STREP virus (with none of the usual symptoms) and it was affecting his immune system/brain connection in an unusual way and causing these odd behaviors. He was given anti-biotics and is essentially fine. There is actually a name for it, a disorder called PANDAS (I looked it up and there is such a thing).
What really bothered me about this segment was the Today Show "Dr." Nancy Snyderman...She is a total hypocrite. She fully supported that this kids OCD was brought on by a virus that affected his immune system and brain and that "those things can happen". But she has repeatedly said in other interviews that it's impossible for Autism to be caused by an immune system - brain connection and the parents who think that are basically crazy.
Gee, kids w/ Autism have all these odd behaviors, gut issues, ear infections, food sensitivities and abnormally functioning brains...but it can't possibly be related to their immune systems (you know...the ones that have been severely altered by vaccinces manufactured to alter the developing immune systems of infants!)
Posted by: DannysVoice | October 12, 2009 at 07:57 PM
No one should consider this takes vaccines off the table.
It's quite possible that the retroviruses, like XMRV, are inherent in the material used to culture the vaccines and are artifacts. Similar to the SV40 virus which came from the kidneys of infected monkeys which were used for polio vaccines.
It could also be that viruses develop from mutations or recombinations of attenuated viruses or live viruses with human cellular RNA within the toxic stew of multivaccines and adjucts.
Viruses use cellular RNA to replicate themselves - such that the vaccine RNA sequences combine with cellular sequences to create new forms in order to survive. The mutation potential of chemicals like thimerosal, aluminum and others may increase the chance of sequence disruptions and recombination.
The problem is if you don't know what it is you don't know what to look for or how to develop a reliable way to find it.
Several viruses have been implicated in CFS before so it will take time to see how this plays out.
Viruses could be yet just another way the symptoms of autism are expressed (autism expression could have more than one cause since it is based on "symptoms").
Posted by: KDM | October 12, 2009 at 07:17 PM
Sooooo much more to learn about (retro) viral reactivation following vaccination
T cell activation and human immunodeficiency virus replication after influenza immunization of infected children - Ramilo et al The Pediatric infectious disease journal 1996, vol. 15, no3, pp. 197-203 (25 ref.) Clin Biochem
Activation of virus replication after vaccination of HIV-1-infected individuals - Staprans SI et al J Exp Med. 1995 Dec 1;182(6):1727-37.
Transient INCREASES in numbers of infectious cells in an HIV-infected chimpanzee following immune stimulation - Fultz PN et al AIDS Res Hum Retroviruses. 1992 Feb;8(2):313-7.
Human immunodeficiency virus-type 1 replication can be increased in peripheral blood of seropositive patients after influenza vaccination. O'Brien WA et al Blood. 1995 Aug 1;86(3):1082-9.
Measles/MMR vaccine for infants born to HIV-positive mothers [Intervention Protocol], B Unnikrishnan et al, The Cochrane Library 2009, Issue 1
Effect of immunization with a common recall antigen on viral expression in patients infected with human immunodeficiency virus type 1 - Stanley SK et al N Engl J Med. 1996 May 9;334(19):1222-30.
The efficiency of acute infection of CD4+ T cells is markedly enhanced in the setting of antigen-specific immune activation - Weissman D et al J Exp Med. 1996 Feb 1;183(2):687-92.
Antigenic stimulation by BCG vaccine as an in vivo driving force for SIV replication and dissemination - Cheynier Really et al. Nat Med. 1998 Apr;4(4):421-7.
Activation by malaria antigens renders mononuclear cells susceptible to HIV infection and re-activates replication of endogenous HIV in cells from HIV-infected adults - Froebel K et al Parasite Immunol. 2004 May;26(5):213-7.
Posted by: Natasa | October 12, 2009 at 07:14 PM
sooo much more to learn about vaccines!
J Clin Invest. 1980 Apr;65(4):798-803.
Adverse effects of cytomegalovirus vaccination in mice.
* Jordan MC.
Studies of live attenuated cytomegalovirus (CMV) vaccine have recently been initiated in man. The possibilities of latent infection and disease resulting from reactivation of vaccine virus are major concerns. Because markers for attenuation of tissue culture-passaged mouse CMV (MCMV) exist, studies of potential adverse effects of vaccination were initiated in mice. Plaque-purified MCMV was passed 12 times in cell culture ("vaccine virus") and shown to be attenuated by virtue of loss of lethality and diminished replication in reticuloendothelial organs of normal mice. Although subcutaneous inoculation of 10(5) plaque-forming units of wild virus was lethal for mice immunosuppressed with antilymphocyte serum (18/18 died), "vaccine MCMV" killed only 3/18 (P < 0.05) and was thus shown to be highly attenuated even in immunosuppressed animals. 4 mo after subcutaneous inoculation of vaccine MCMV, no infectious virus was detectable in the tissues of normal C(3)H mice. However, immunosuppression with anti-lymphocyte serum and cortisone caused MCMV reactivation, dissemination, and wide-spread cytomegalic inclusion disease in 19 of 20 animals. Characterization of the reactivating virus recovered from salivary glands indicated that reversion to virulence had occurred. Thus, vaccine MCMV, although markedly attenuated initially, established latent infection, reactivated after immunosuppression, and reverted to virulence, at least in salivary gland tissue. These data from the murine model substantiate the need for careful surveillance and virologic study of patients given experimental CMV vaccine. PMID: 6244333 [PubMed - indexed for MEDLINE
so much more to learn....
Posted by: Natasa | October 12, 2009 at 07:08 PM
Can someone help me better understand what the results of this study really mean (in simplest layman's terms) and what it might mean for possible treatment? Is this something my son can be tested for?
Thanks in advance for any explanatory replies!
Posted by: Donna Alvado | October 12, 2009 at 07:05 PM
Amy Becker Clark wrote: "I highly recommend the book "Osler's Web, Inside the Labyrinth of the Chronic Fatigue Syndrome Epidemic" by Hillary Johnson. The parallels between autism and CFS/ME extend far beyond a viral etiology: both epidemics are plagued by political and intellectual bungling so outrageous you'd almost think it was by design. Almost..."
The same is true of Lyme disease. The Infectious Diseases Society of America (IDSA) has done a HUGE coverup of Lyme disease, and doesn't even acknowledge the existence of chronic Lyme. "Cure Unknown" is a good book about this.
Posted by: Shannon | October 12, 2009 at 06:36 PM
Nobody believed me when i posted on our yahoogroup, that this must be a tick borne transmittable...as in LYME DISEASE folks...ticks can carry VIRUSES...the vector is BROWN MICE and DEER TICKS...
This exciting news may have implications for people with Lyme disease. It is a "murine" (mouse) retrovirus. We all know that ticks feed on mice. They don't know yet if ticks are vectors of this retrovirus, but if they are, they could pass it to humans along with all the other tick-borne infections they carry. Whether ticks transmit it or not, the presence of this retrovirus may explain some cases of treatment-resistant Lyme disease. We won't know until they develop a commercial test. And then treatment is a whole new ball game. We hope this discovery translates quickly into relief for people with intractable fatigue.
I started a group a couple of years back which found that kids with autism HAD LYME. What kidn of lyme, what type was interesting...because many would not seroconvert the antibodies, due to their immune dysregulation. But, when they get on ABX's the borrelia drive to the serum and they light up like christmas lights.
I also mainttained, that lyme is comgin FROM THE PARENTS. The mothers ofte have fatiguing illnesses. They are sick with lyme, and passing it to their children.
David, I emailed you, and there were no replies years ago. Perhaps you should have read that email....
Interestingly, the highest lyme states, have the highest rates of lyme disease...is it any wonder when you superimpose the maps of incidence, they exactly match?
What more do DAN doctors need? They need to be starting now to testing kids with autism for lyme...which by the way, is increasing, as much as autism is.
Lyme can mimic over four hundred diseases, some of them can be very innocuous...some are debilitiating and life threatening.
If this comes to light, we should get the DAN doctors with the LIA FOUNDATION, to wake them up to some certain facts...a small thing called FAMILIAL BORRELISOIS, would hamper the argument that autism runs in families...no....lyme does....and the inability to detox....
Posted by: Kathy Blanco | October 12, 2009 at 06:00 PM
I highly recommend the book "Osler's Web, Inside the Labyrinth of the Chronic Fatigue Syndrome Epidemic" by Hillary Johnson. The parallels between autism and CFS/ME extend far beyond a viral etiology: both epidemics are plagued by political and intellectual bungling so outrageous you'd almost think it was by design. Almost...
Posted by: Amy Becker Clark | October 12, 2009 at 05:48 PM
I think that my two children, my husband, my sister-in-law has something wrong with their immune system when it comes to fighting off a virus. They do okay, but they run higher temperatures than anyone else. They are sicker longer too. They always have sinus infections - always a viral sinus infection.
However the vitamin D 2000 iu seems to really made a difference in the severity of the sinus infection.
Posted by: Benedetta | October 12, 2009 at 05:37 PM
It's the old question of which came first, the chicken or the egg.
Maybe that specific virus helps to cause autism.
Or maybe the various health problems -- which come along with, say, mercury poisoning, or an excess of toxic substances in vaccinations -- maybe that sets up a condition which allows this particular virus to flourish.
They'll never know, will they? Because they'll keep working on the "virus caused it" idea.
To the man with a hammer, every problem is a nail.
Posted by: P. Jennings | October 12, 2009 at 04:25 PM
Sorry but this sounds likes smokescreen to me. Now that the "it's just genetic" argument has become untenable. An attempt to get vaccines off the hook and explain why many autistic children improve with antivirals. How prevalent is this virus in the general population? Do you find it in people with a functioning immune system.
Did they look for measels RNA, too?
Posted by: julie | October 12, 2009 at 04:23 PM
I have always suspected this to be the case.
It could be why our son is such a tough nut to crack and only make small or moderate gains with most biomeds (methylB12 and vitamin A have really helped him).
Posted by: KDM | October 12, 2009 at 04:09 PM