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=20
Institute in Reno, NV along with The Cleveland Clinic and the National=20
Cancer Institute (NIH) is the first convincing association of an=20
isolated retrovirus with CFS. The gammaretrovirus XMRV was only recently=20
discovered in 2007 at the Cleveland Clinic[ii] and cultured out of=20
prostate cancer tissue from prostate cancer victims who had a rare=20
mutation in the anti-viral RNase-L pathway. CFS patients also have=20
unusual alterations in the same anti-viral pathway (1997)[iii] though=20
different in its detail and far less rare.
Dan Peterson MD, a long time resident of Incline Village, NV (Lake=20
Tahoe) and I worked for over eight years (1984-1992) to link CFS to a=20
retrovirus. Dan first sent five CFS patient samples to Specialty Labs in=20
1985 to test for HTLV-1 and 4 of 5 were positive. We did this due to=20
incredible disturbances on flow cytometry of peripheral mononuclear=20
cells producing elevated CD4/CD8 ratios due to CD8 depletion as well as=20
scatter patterns (debris patterns) that the laboratory flow cytometrist=20
said she had only seen in HIV infections.
A radiologist at UC San Diego, on review, said our MRI brain scans done=20
on CFS cases showing UBO's (1988)[iv], looked exactly likes AIDS cases.=20
Repeat testing was negative for HTLV-1 and Dr. James Peters of Specialty=20
Labs suggested these CFS patients might have a cross reacting and novel=20
retrovirus that looks like HTLV-1.
In 1986, I called the NCI and Robert Gallo MD, head of the foremost=20
retrovirology laboratory in the world at the time, accepted Lake Tahoe=20
samples for a year resulting in the association of an HHV-6A strain with=20
Lake Tahoe CFS cases (1992)[v], only previously linked to HIV infection.
While practicing in Charlotte, NC and based on continued evidence of=20
unusual immune disturbances by flow cytometry including CD4 depletion=20
(ICL) in 15% of CFS patients which was investigated in my clinic and=20
dismissed by the CDC in 1991 and continued high RNase-L activity=20
(1994)[vi], I contacted Elaine DeFreitas PhD at the Wistar Institute in=20
Philadelphia at the University of Pennsylvania who ultimately found=20
HTLV-II-like genes associated with CFS (1991)[vii]. Her work was=20
unfortunately assaulted by the CDC that claimed either an endogenous RV=20
sequence that lighted up in cases and controls using her primers (per=20
Dr. J.W. Gow) or null responses to cases and controls (per CDC scientist).
Elaine argued that these two scientists with diametrically opposing=20
results manipulated the magnesium concentration which affects the primer=20
stringency and got whatever result they wanted, to make their opposite=20
claims. Her proposal to fly CDC scientists to Philadelphia to run the=20
assays side by side with the her in her lab to see if these results=20
could be replicated was dismissed by the CDC based on =93lack of funds to=
=20
buy plane tickets=94 from Atlanta to Philadelphia. Dr. Gow would later=20
publish his opinion (1992)[viii]. Left unfunded by senior administrators=20
at the NIH and the CDC, the search for a retroviral link in CFS=20
dissipated and was lost until Judy Mikovits PhD, operating out of the=20
independent Whittemore-Peterson Institute, revived the long search. I=20
congratulate her and the Whittemore-Peterson Institute.
The finding of antibody or active virus in 95% of CFS and 4% of controls=20
is a result that argues for causality, in my opinion, especially with=20
the associated RNase-L[ix] corruption and NK functional impairment[x]=20
that might predict such an infection. This novel retrovirus could easily=20
shift the redox state just like HIV as has been published in (2001)[xi]=20
and (1995)[xii] and induce all manner of associated pathogens as seen in=20
CFS[xiii],[xiv],[xv],[xvi],[xvii]. A redox shift could ultimately=20
corrupt the gut ecology and create P450 decoupling based on NADPH=20
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=20
also think this virus is infectious with at least ten million Americans=20
infected who appear healthy and perhaps another 4 million Americans or=20
more with CFS as recently estimated by the CDC (2007)[xviii]. However,=20
disease expression may be more limited causing the illusion that it is=20
not infectious. Furthermore, there may be other diseases that are=20
similar and dissimilar to CFS that are associated with if not caused by=20
XMRV.
------------------------------------------------------------------------
[i] Vincent C. Lombardi,1* Francis W. Ruscetti,2* Jaydip Das Gupta,3 Max=20
A. Pfost,1 Kathryn S. Hagen,1 Daniel L. Peterson,1 Sandra K. Ruscetti,4=20
Rachel K. Bagni,5 Cari Petrow-Sadowski,6 Bert Gold,2 Michael Dean,2=20
Robert H. Silverman,3 Judy A. Mikovits1=86 =93Detection of an Infectious=20
Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue=20
Syndrome=94 Science =96 epub ahead of publication - 8 October 2009, pp 4-=
10,=20
science.1179052, www.sciencexpress.org
[ii] Dong B, Kim S, Hong S, Das Gupta J, Malathi K, Klein EA, Ganem D,=20
Derisi JL, Chow SA, Silverman RH =93An infectious retrovirus susceptible=20
to an IFN antiviral pathway from Human prostate tumors=94 (2007) Proc Nat=
l=20
Acad Sci USA 104:1655=961660.
[iii] Suhadolnick RJ, Peterson DL, O'Brien K, Cheney PR, Herst CVT,=20
Reichenbach NL, Kon N, Horvath SE, Iacono KT, Adelson ME, De Meirleir K,=20
De Becker P, Charubala R and Pfleiderer W "Biochemical Evidence for a=20
Novel Low Molecular Weight 2-5A-Dependent RNase L in Chronic Fatigue=20
Syndrome" Journal of Inteferon and Cytokine Research 17:377-385 (1997)
[iv] Buchwald D, Biddle R, Josesz FA, Kikinis R, Cheney PR, Peterson D,=20
Komaroff AL, =93Central Nervous System Abnormalities on Magnetic Resonanc=
e=20
Imaging (MRI) in an Outbreak of Chronic Fatigue Syndrome (CFS)=94,=20
Presented at the American Federation for Clinical Research Annual=20
Meeting, San Diego, CA 1988
[v] Buchwald,D., Cheney, PR., Peterson,DL., Henry,B., Wormsley,SB.,=20
Geiger,A., Ablashi,DV., Salahuddin,Z., Saxinger,C., Biddle,R.,=20
Kikinis,R., Jolesz,FA., Folks,T., Balachandran,N., Peter,JB.,=20
Gallo,RC.,and Komaroff,AL., =93A Chronic Illness Characterized by Fatigue=
,=20
Neurologic and Immunologic Disorders, and Active Human Herpesvirus-6=20
Infection=94, Annals of Internal Medicine, Jan. 15, 1992:116(2), pp.103-1=
13.
[vi] Suhadolnik, RJ., Reichenbach,NL., Hitzges,P., Adelson,ME.,=20
Peterson,DL., Cheney, PR., Salvato,P., Thompson,C., Loveless,M.,=20
Muller,WG., Schroder,HC., Strayer,DR., and Carter,WA., "Changes in the=20
2-5A Synthetase/RNase L Antiviral Pathway in a Controlled Clinical Trial=20
with Poly(1)-Poly(C12U) in Chronic Fatigue Syndrome", In Vivo,=20
8:599-604, (1994).
[vii] Buchwald,D., Cheney, PR., Peterson,DL., Henry,B., Wormsley,SB.,=20
Geiger,A., Ablashi,DV., Salahuddin,Z., Saxinger,C., Biddle,R.,=20
Kikinis,R., Jolesz,FA., Folks,T., Balachandran,N., Peter,JB.,=20
Gallo,RC.,and Komaroff,AL., =93A Chronic Illness Characterized by Fatigue=
,=20
Neurologic and Immunologic Disorders, and Active Human Herpesvirus-6=20
Infection=94, Annals of Internal Medicine, Jan. 15, 1992:116(2), pp.103-1=
13.
[viii] J W Gow, K Simpson, A Schliephake, W M Behan, L J Morrison, H=20
Cavanagh, A Rethwilm, P O Behan =93Search for retrovirus in the chronic=20
fatigue syndrome=94 Journal of Clinical Pathology 1992;45:1058-1061
[ix] Suhadolnick RJ, Peterson DL, O'Brien K, Cheney PR, Herst CVT,=20
Reichenbach NL, Kon N, Horvath SE, Iacono KT, Adelson ME, De Meirleir K,=20
De Becker P, Charubala R and Pfleiderer W "Biochemical Evidence for a=20
Novel Low Molecular Weight 2-5A-Dependent RNase L in Chronic Fatigue=20
Syndrome" Journal of Inteferon and Cytokine Research 17:377-385 (1997)
[x] Caligiuri M, Murry C, Buchwald D, Levine H, Cheney PR, Peterson DL,=20
Komaroff AL, and Ritz R, =93Phenotypic and Functional Deficiency of=20
Natural Killer Cells in Patients with Chronic Fatigue Syndrome=94. J=20
Immunology 1987; 139: 3306-
[xi] Ricard MJ, Favier A et al =93HIV-1 Tat protein impairs=20
selenoglutathione peroxidase expression by a mechanism independent of=20
cellular selemium uptake: consequences on cellular resistance to UV=20
radiation. Arch Biochem Biophys. 2001 Feb 15: 386(2):213-20
[xii] Westendorp MO, Lehmann V et al =96 German Cancer Research Center,=20
Heidelberg) =93HIV-1 Tat gene activates NF-kB via TNF-a and associated=20
with reduced MnSOD and GSH/GSSG ratio=94 EMBO J. 1995 Feb 1: 14(3):546-54
[xiii] Buchwald,D., Cheney, PR., Peterson,DL., Henry,B., Wormsley,SB.,=20
Geiger,A., Ablashi,DV., Salahuddin,Z., Saxinger,C., Biddle,R.,=20
Kikinis,R., Jolesz,FA., Folks,T., Balachandran,N., Peter,JB.,=20
Gallo,RC.,and Komaroff,AL., =93A Chronic Illness Characterized by Fatigue=
,=20
Neurologic and Immunologic Disorders, and Active Human Herpesvirus-6=20
Infection=94, Annals of Internal Medicine, Jan. 15, 1992:116(2), pp.103-1=
13.
[xiv] Straus,SE., Tosato,G., Armstrong,G., Lawley,T., Preble,OT.,=20
Henle,W., Davey,R., Pearson,G.,
Epstein,J., Brus,I. and Blaese,RM., =93Persisting Illness and Fatigue in=20
Adults with Evidence of Epstein-Barr
Virus Infection=94, Ann. Intern. Med.,102:7-16,1985.
[xv] W. John Martin, Li Cheng Zeng, Khalid Ahmed, Maju Roy,=20
"Cytomegalovirus - Related Sequence in a Atypical Cytopathic Virus=20
Repeatedly Isolated From a Patient with Chronic Fatigue Syndrome",=20
American Journal of Pathology, pgs. 440-451, Volume 145:(2), August,1994.
[xvi] Gow,JW., Behan,WMH., Clements,GB., Woodall,C., Riding,M.,=20
Behan,PO., =93Enteroviral RNA Sequences Detected by Polymerase Chain=20
Reaction in Muscle of Patients with Postviral Fatigue Syndrome=94,Br. Med=
.=20
J.,302:692-96,1991.
[xvii] Multiple co-infections (Mycoplasma, Chlamydia, human herpes=20
virus-6) in blood of chronic fatigue syndrome patients: association with=20
signs and symptoms. G. L. Nicolson et al., Acta Pathol. Microbiol.=20
Immunol. Scand.(APMIS) 2003; 111: 557-566
[xviii] Reeves WC, Jones JJ, Maloney E, et al (CDC). New study on the=20
prevalence of CFS in metro, urban and rural Georgia populations.=20
Population Health Metrics. 2007; 5(5).
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