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

  [ 26 votes ]   [ Discuss This Article ]
www.ProHealth.com • January 3, 1994


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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