Previous studies from this laboratory have demonstrated a statistically significant dysregulation in several key components of the 2',5'-oligoadenylate (2-5A) synthetase/RNase L and PKR antiviral pathways in chronic fatigue syndrome (CFS) (Suhadolnik et al. Clin Infect Dis 18, S96-104, 1994; Suhadolnik et al. In Vivo 8, 599-604, 1994). Two methodologies have been developed to further examine th...

BACKGROUND Although several studies have confirmed the association of xenotropic murine leukemia virus-related virus (XMRV) and prostate cancer, this association is still controversial, as most studies did not detect XMRV in prostate tissue samples. Furthermore, some genetic and epidemiological studies have highlighted a role for RNase L polymorphisms, particularly R462Q, in the progression of ...

Alkaline ribonuclease (RNase; EC 3.1.27.5) activities and 2',5'-oligoadenylate synthetase (2-5 AS; no EC no. assigned) activities in serum were measured in nine patients with hepatitis B e antigen-positive chronic hepatitis B before, during, and after treatment with recombinant human interferon alpha-2b for four weeks at daily doses ranging from 3 to 10 mega-units. Alkaline RNase activities in ...

Upon infection, cellsof higher vertebratesproduce interferons (IFNs),whichactivate variousantiviral programs in the infectedcell andsurroundingcells, thus limiting the spreadof infection.Oneof these antiviral mediators is RNase L, an endoribonuclease that cleaves viral and cellular RNA on demand. RNase L is activated by 2’,5’-linked oligoadenylates (2-5A), products of IFN-inducible 2-5A synthet...

2'-5'oligoadenylate-dependent ribonuclease L (RNase L) is one of the key enzymes involved in the function of interferons (IFNs), a family of cytokines participating in innate immunity against viruses and other microbial pathogens. Upon binding with its activator, 5'-phosphorylated, 2'-5' linked oligoadenylates (2-5A), RNase L degrades single-stranded viral and cellular RNAs and thus plays an im...

Virus replication in higher vertebrates is restrained by IFNs that cause cells to transcribe genes encoding antiviral proteins, such as 2'-5' oligoadenylate synthetases. 2'-5' oligoadenylate synthetase is stimulated by dsRNA to produce 5'-phosphorylated, 2'-5'-linked oligoadenylates (2-5A), whose function is to activate RNase L. Although RNase L is required for a complete IFN antiviral response...

Cellular translation is inhibited following infection with most strains of reovirus, but the mechanisms responsible for this phenomenon remain to be elucidated. The extent of host shutoff varies in a strain-dependent manner; infection with the majority of strains leads to strong host shutoff, while infection with strain Dearing results in minimal inhibition of cellular translation. A genetic st...

The interferon inducible oligoadenylate synthetase (OAS)/RNase L pathway is an innate defense against invading viral pathogens that is linked to cell survival [reviewed in 1]. OAS family proteins are pattern recognition receptors that recognize double-stranded RNA (dsRNA), a pathogen-associated molecular pattern. In the presence of dsRNA, which is produced during the replication cycle of a broa...

RNase L is activated by 2',5'-oligoadenylates (2-5A) at subnanomolar levels to cleave single-stranded RNA. We previously reported the hypothesis that the introduction of an 8-methyladenosine residue at the 2'-terminus of the 2-5A tetramer shifts the 2-5A binding site of RNase L. In this study, we synthesized various 5'-modified 2-5A analogs with 8-methyladenosine at the 2'-terminus. The doxiflu...

The nucleotide sequence analysis of tRNA has required (a) identification of fragments isolated from complete digestion with pancreatic RNase and RNase T1 and, in addition, (b) the analysis of large oligonucleotide fragments produced by partial digestion with RNase T1 (l-4) and, in some cases, partial digestion with pancreatic RNase (5). In continuation of the work reported in the preceding pape...