PMID- 8148461
OWN - NLM
STAT- MEDLINE
DCOM- 19940512
LR  - 20220225
IS  - 1058-4838 (Print)
IS  - 1058-4838 (Linking)
VI  - 18 Suppl 1
DP  - 1994 Jan
TI  - Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with 
      chronic fatigue syndrome.
PG  - S96-104
AB  - 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.
FAU - Suhadolnik, R J
AU  - Suhadolnik RJ
AD  - Department of Biochemistry, Temple University School of Medicine, Philadelphia, 
      Pennsylvania 19140.
FAU - Reichenbach, N L
AU  - Reichenbach NL
FAU - Hitzges, P
AU  - Hitzges P
FAU - Sobol, R W
AU  - Sobol RW
FAU - Peterson, D L
AU  - Peterson DL
FAU - Henry, B
AU  - Henry B
FAU - Ablashi, D V
AU  - Ablashi DV
FAU - Muller, W E
AU  - Muller WE
FAU - Schroder, H C
AU  - Schroder HC
FAU - Carter, W A
AU  - Carter WA
AU  - et al.
LA  - eng
GR  - P01 CA-29545/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Adenine Nucleotides)
RN  - 0 (Antiviral Agents)
RN  - 0 (Oligoribonucleotides)
RN  - 0 (RNA, Double-Stranded)
RN  - 27416-86-0 (Poly U)
RN  - 61172-40-5 (2',5'-oligoadenylate)
RN  - 94325AJ25N (poly(I).poly(c12,U))
RN  - EC 2.7.7.84 (2',5'-Oligoadenylate Synthetase)
RN  - EC 3.1.- (Endoribonucleases)
RN  - EC 3.1.26.- (2-5A-dependent ribonuclease)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - 2',5'-Oligoadenylate Synthetase/*metabolism
MH  - Adenine Nucleotides/metabolism
MH  - Antiviral Agents/therapeutic use
MH  - Endoribonucleases/*metabolism
MH  - Fatigue Syndrome, Chronic/drug therapy/etiology/*metabolism
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Oligoribonucleotides/metabolism
MH  - Poly I-C/therapeutic use
MH  - Poly U/therapeutic use
MH  - RNA, Double-Stranded/therapeutic use
MH  - Up-Regulation
MH  - Virus Diseases/complications/drug therapy/*metabolism
EDAT- 1994/01/01 00:00
MHDA- 1994/01/01 00:01
CRDT- 1994/01/01 00:00
PHST- 1994/01/01 00:00 [pubmed]
PHST- 1994/01/01 00:01 [medline]
PHST- 1994/01/01 00:00 [entrez]
AID - 10.1093/clinids/18.supplement_1.s96 [doi]
PST - ppublish
SO  - Clin Infect Dis. 1994 Jan;18 Suppl 1:S96-104. doi: 
      10.1093/clinids/18.supplement_1.s96.