NB: The online copy of the print edition report uses the same headline as the longer article published online on 8 October: Chronic fatigue syndrome linked to ‘cancer virus’
It’s item 3 of 3 in that slot which may means its on between 2.30-3pm.
Don’t forget one can ring in to ask a question (and maybe make a point at the same time!?)
Taped Oct. 12th 2009 in her office. Dr Klimas talks about XMRV, what it means, what’s next and what you can do.
A retrovirus XMRV is linked to Chronic Fatigue Syndrome
Paul R. Cheney MD, PhD
The Cheney Clinic, Asheville, NC
October 2009
www.cheneyresearch.com
www.cheneyclinic.com
Recently published in Science (2009)[i] out of the Whittemore-Peterson Institute in Reno, NV along with The Cleveland Clinic and the National Cancer Institute (NIH) is the first convincing association of an isolated retrovirus with CFS. The gammaretrovirus XMRV was only recently discovered in 2007 at the Cleveland Clinic[ii] and cultured out of prostate cancer tissue from prostate cancer victims who had a rare mutation in the anti-viral RNase-L pathway. CFS patients also have unusual alterations in the same anti-viral pathway (1997)[iii] though different in its detail and far less rare.
Dan Peterson MD, a long time resident of Incline Village, NV (Lake Tahoe) and I worked for over eight years (1984 1992) to link CFS to a retrovirus. Dan first sent five CFS patient samples to Specialty Labs in 1985 to test for HTLV-1 and 4 of 5 were positive. We did this due to incredible disturbances on flow cytometry of peripheral mononuclear cells producing elevated CD4/CD8 ratios due to CD8 depletion as well as scatter patterns (debris patterns) that the laboratory flow cytometrist said she had only seen in HIV infections.
A radiologist at UC San Diego, on review, said our MRI brain scans done on CFS cases showing UBO’s (1988)[iv], looked exactly likes AIDS cases. Repeat testing was negative for HTLV-1 and Dr. James Peters of Specialty Labs suggested these CFS patients might have a cross reacting and novel retrovirus that looks like HTLV-1.
In 1986, I called the NCI and Robert Gallo MD, head of the foremost retrovirology laboratory in the world at the time, accepted Lake Tahoe samples for a year resulting in the association of an HHV-6A strain with Lake Tahoe CFS cases (1992)[v], only previously linked to HIV infection.
While practicing in Charlotte, NC and based on continued evidence of unusual immune disturbances by flow cytometry including CD4 depletion (ICL) in 15% of CFS patients which was investigated in my clinic and dismissed by the CDC in 1991 and continued high RNase-L activity (1994)[vi], I contacted Elaine DeFreitas PhD at the Wistar Institute in Philadelphia at the University of Pennsylvania who ultimately found HTLV-II-like genes associated with CFS (1991)[vii]. Her work was unfortunately assaulted by the CDC that claimed either an endogenous RV sequence that lighted up in cases and controls using her primers (per Dr. J.W. Gow) or null responses to cases and controls (per CDC scientist).
Elaine argued that these two scientists with diametrically opposing results manipulated the magnesium concentration which affects the primer stringency and got whatever result they wanted, to make their opposite claims. Her proposal to fly CDC scientists to Philadelphia to run the assays side by side with the her in her lab to see if these results could be replicated was dismissed by the CDC based on “lack of funds to buy plane tickets” from Atlanta to Philadelphia. Dr. Gow would later publish his opinion (1992)[viii]. Left unfunded by senior administrators at the NIH and the CDC, the search for a retroviral link in CFS dissipated and was lost until Judy Mikovits PhD, operating out of the independent Whittemore-Peterson Institute, revived the long search. I congratulate her and the Whittemore-Peterson Institute.
The finding of antibody or active virus in 95% of CFS and 4% of controls is a result that argues for causality, in my opinion, especially with the associated RNase-L[ix] corruption and NK functional impairment[x] that might predict such an infection. This novel retrovirus could easily shift the redox state just like HIV as has been published in (2001)[xi] and (1995)[xii] and induce all manner of associated pathogens as seen in CFS[xiii],[xiv],[xv],[xvi],[xvii]. A redox shift could ultimately corrupt the gut ecology and create P450 decoupling based on NADPH depletion observed in CFS and lead to environmental illness as well.
Time will tell but I think Dr. Mikovits is right to suspect causality. I also think this virus is infectious with at least ten million Americans infected who appear healthy and perhaps another 4 million Americans or more with CFS as recently estimated by the CDC (2007)[xviii]. However, disease expression may be more limited causing the illusion that it is not infectious. Furthermore, there may be other diseases that are similar and dissimilar to CFS that are associated with if not caused by XMRV.
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[i] Vincent C. Lombardi,1* Francis W. Ruscetti,2* Jaydip Das Gupta,3 Max A. Pfost,1 Kathryn S. Hagen,1 Daniel L. Peterson,1 Sandra K. Ruscetti,4 Rachel K. Bagni,5 Cari Petrow-Sadowski,6 Bert Gold,2 Michael Dean,2 Robert H. Silverman,3 Judy A. Mikovits1† “Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome” Science – epub ahead of publication – 8 October 2009, pp 4-10, science.1179052, www.sciencexpress.org
[ii] Dong B, Kim S, Hong S, Das Gupta J, Malathi K, Klein EA, Ganem D, Derisi JL, Chow SA, Silverman RH “An infectious retrovirus susceptible to an IFN antiviral pathway from Human prostate tumors” (2007) Proc Natl Acad Sci USA 104:1655–1660.
[iii] Suhadolnick RJ, Peterson DL, O’Brien K, Cheney PR, Herst CVT, Reichenbach NL, Kon N, Horvath SE, Iacono KT, Adelson ME, De Meirleir K, De Becker P, Charubala R and Pfleiderer W “Biochemical Evidence for a Novel Low Molecular Weight 2-5A-Dependent RNase L in Chronic Fatigue Syndrome” Journal of Inteferon and Cytokine Research 17:377-385 (1997)
[iv] Buchwald D, Biddle R, Josesz FA, Kikinis R, Cheney PR, Peterson D, Komaroff AL, “Central Nervous System Abnormalities on Magnetic Resonance Imaging (MRI) in an Outbreak of Chronic Fatigue Syndrome (CFS)”, Presented at the American Federation for Clinical Research Annual Meeting, San Diego, CA 1988
[v] Buchwald,D., Cheney, PR., Peterson,DL., Henry,B., Wormsley,SB., Geiger,A., Ablashi,DV., Salahuddin,Z., Saxinger,C., Biddle,R., Kikinis,R., Jolesz,FA., Folks,T., Balachandran,N., Peter,JB., Gallo,RC.,and Komaroff,AL., “A Chronic Illness Characterized by Fatigue, Neurologic and Immunologic Disorders, and Active Human Herpesvirus-6 Infection”, Annals of Internal Medicine, Jan. 15, 1992:11 (2), pp.103-113.
[vi] Suhadolnik, RJ., Reichenbach,NL., Hitzges,P., Adelson,ME., Peterson,DL., Cheney, PR., Salvato,P., Thompson,C., Loveless,M., Muller,WG., Schroder,HC., Strayer,DR., and Carter,WA., “Changes in the 2-5A Synthetase/RNase L Antiviral Pathway in a Controlled Clinical Trial with Poly(1)-Poly(C12U) in Chronic Fatigue Syndrome”, In Vivo, 8:599-604, (1994).
[vii] Buchwald,D., Cheney, PR., Peterson,DL., Henry,B., Wormsley,SB., Geiger,A., Ablashi,DV., Salahuddin,Z., Saxinger,C., Biddle,R., Kikinis,R., Jolesz,FA., Folks,T., Balachandran,N., Peter,JB., Gallo,RC.,and Komaroff,AL., “A Chronic Illness Characterized by Fatigue, Neurologic and Immunologic Disorders, and Active Human Herpesvirus-6 Infection”, Annals of Internal Medicine, Jan. 15, 1992:11 (2), pp.103-113.
[viii] J W Gow, K Simpson, A Schliephake, W M Behan, L J Morrison, H Cavanagh, A Rethwilm, P O Behan “Search for retrovirus in the chronic fatigue syndrome” Journal of Clinical Pathology 1992;45:1058 1061
[ix] Suhadolnick RJ, Peterson DL, O’Brien K, Cheney PR, Herst CVT, Reichenbach NL, Kon N, Horvath SE, Iacono KT, Adelson ME, De Meirleir K, De Becker P, Charubala R and Pfleiderer W “Biochemical Evidence for a Novel Low Molecular Weight 2-5A-Dependent RNase L in Chronic Fatigue Syndrome” Journal of Inteferon and Cytokine Research 17:377-385 (1997)
[x] Caligiuri M, Murry C, Buchwald D, Levine H, Cheney PR, Peterson DL, Komaroff AL, and Ritz R, “Phenotypic and Functional Deficiency of Natural Killer Cells in Patients with Chronic Fatigue Syndrome”. J Immunology 1987; 139: 3306-
[xi] Ricard MJ, Favier A et al “HIV-1 Tat protein impairs selenoglutathione peroxidase expression by a mechanism independent of cellular selemium uptake: consequences on cellular resistance to UV radiation. Arch Biochem Biophys. 2001 Feb 15: 386(2):213-20
[xii] Westendorp MO, Lehmann V et al – German Cancer Research Center, Heidelberg) “HIV-1 Tat gene activates NF-kB via TNF-a and associated with reduced MnSOD and GSH/GSSG ratio” EMBO J. 1995 Feb 1: 14(3):546-54
[xiii] Buchwald,D., Cheney, PR., Peterson,DL., Henry,B., Wormsley,SB., Geiger,A., Ablashi,DV., Salahuddin,Z., Saxinger,C., Biddle,R., Kikinis,R., Jolesz,FA., Folks,T., Balachandran,N., Peter,JB., Gallo,RC.,and Komaroff,AL., “A Chronic Illness Characterized by Fatigue, Neurologic and Immunologic Disorders, and Active Human Herpesvirus-6 Infection”, Annals of Internal Medicine, Jan. 15, 1992:116 (2), pp.103-113.
[xiv] Straus,SE., Tosato,G., Armstrong,G., Lawley,T., Preble,OT., Henle,W., Davey,R., Pearson,G., Epstein,J., Brus,I. and Blaese,RM., “Persisting Illness and Fatigue in Adults with Evidence of Epstein Barr Virus Infection”, Ann. Intern. Med.,102:7-16,1985.
[xv] W. John Martin, Li Cheng Zeng, Khalid Ahmed, Maju Roy, “Cytomegalovirus – Related Sequence in a Atypical Cytopathic Virus Repeatedly Isolated From a Patient with Chronic Fatigue Syndrome”, American Journal of Pathology, pgs. 440-451, Volume 145:(2), August,1994.
[xvi] Gow,JW., Behan,WMH., Clements,GB., Woodall,C., Riding,M., Behan,PO., “Enteroviral RNA Sequences Detected by Polymerase Chain Reaction in Muscle of Patients with Postviral Fatigue Syndrome”,Br. Med. J.,302:692-96,1991.
[xvii] Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms. G. L. Nicolson et al., Acta Pathol. Microbiol. Immunol. Scand.(APMIS) 2003; 111: 557-566
[xviii] Reeves WC, Jones JJ, Maloney E, et al (CDC). New study on the prevalence of CFS in metro, urban and rural Georgia populations. Population Health Metrics. 2007; 5(5).
Lets revive the Lyndonville research group again (gasp). I would like to test the original Lyndonville kids for XMRV, and if any of you reading this became ill in the Lyndonville area around 1985, were 18 or under at the time, and want to be evaluated, please write to me at lynnews@davidsbell.com . Even if you are feeling great now.
If you know anyone that falls into this category, please send the information to them so they can get in touch with Dr. Bell directly.
