Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with Chronic Fatigue Syndrome (CFS)

Levels of 2′,5′-oligoadenylate (2-5A) synthetase, bioactive

2-5A, and RNase L were measured in extracts of peripheral

blood mononuclear cells (PBMCs) from 15 individuals with

chronic fatigue syndrome (CFS) before and during therapy with

the biological response modifier poly(I).poly(C12U) and were

compared with levels in healthy controls. Patients differed

significantly from controls in having a lower mean basal level

of latent 2-5A synthetase (P < .0001), a higher pretreatment
level of bioactive 2-5A (P = .002), and a higher level of

pretherapy RNase L activity (P < .0001). PBMC extracts from 10
persons with CFS had a mean basal level of activated 2-5A

synthetase higher than the corresponding control value (P =

.009). All seven pretherapy PBMC extracts tested were positive

for the replication of human herpesvirus 6 (HHV-6). Therapy

with poly(I).poly(C12U) resulted in a significant decrease in

HHV-6 activity (P < .01) and in downregulation of the 2-5A
synthetase/RNase L pathway in temporal association with

clinical and neuropsychological improvement. The upregulated

2-5A pathway in CFS before therapy is consistent with an

activated immune state and a role for persistent viral

infection in the pathogenesis of CFS. The response to therapy

suggests direct or indirect antiviral activity of

poly(I).poly(C12U) in this situation.

Suhadolnik RJ, Reichenbach NL, Hitzges P, Sobol RW, Peterson DL,

Henry B, Ablashi DV, Muller WE, Schroder HC, Carter WA, et al

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