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DsRNA

Interferon (IFN) differs from bona fide antiviral diugs since it is a natural defense protein of the host organism and does not directly interfere with the viral replication steps. Interferons are small glycoproteins inducing immune modulatory and antiviral activities. They are secreted by lymphocytes, leukocytes and fibroblasts in response to foreign nucleic acids (dsRNA). [Pg.197]

An additional pathway leading to very efficient EFN-(3 responses involves one of the Toll-like-recqDtors (TLR), TLR3 which also senses dsRNA and is mainly expressed in dendritic cells (DC) and macrophages. Signal transduction then proceeds via the adaptor molecule TICAM/TRIF associated with the TER.-domain of... [Pg.639]

Recently, the related phenomenon of RNA interference (RNAi) has attracted much attention [5]. RNAi occurs when a short (generally 21 nucleotides in length) double-stranded RNA (dsRNA) catalyticaUy represses the translation of a fully complementary mRNA sequence. The process appears to proceed via a complex formed between the antisense RNA strand and a protein with RNase activity [6]. Upon binding to the target mRNA sequence, the ribonucleoprotein complex initiates cleavage of the mRNA transcript thus preventing translation of intact protein. After dissociation from the truncated mRNAs, the ribonucleoprotein complex is free to act on other intact mRNAs. Such small interfering RNAs (siRNAs) have... [Pg.193]

The sole biochemical function of 2 -5A (and hence 2 -5 A synthetase) appears to be as an activator of a dormant endo-RNase, which is expressed constitutively in the cell. This RNase, known as RNase L or RNase F, cleaves all types of single-stranded RNA (ssRNA). This inhibits production of both viral and cellular proteins, thus paralyzing viral replication. Presumably, cellular destruction of the invading ssRNA will be accompanied by destruction of any additional viral components. Removal of dsRNA would facilitate deactivation of the endo-RNase, allowing translation of cellular mRNA to resume. A 2-5 phosphodiesterase represents a third enzymatic... [Pg.220]

Exposure of cells to interferon normally results in the induction of a protein kinase termed eIF-2a protein kinase. The enzyme, which is synthesized in a catalytically inactive form, is activated by exposure to dsRNA. The activated kinase then phosplorylates its substrate, i.e. eIF-2a, which is the smallest subunit of initiation factor 2 (eIF2). This, in turn, blocks construction of the smaller ribosomal subunit, thereby preventing translation of all viral (and cellular) mRNA (Figure 8.6). [Pg.222]

RNAi technology has obvious therapeutic potential as an antisense agent, and initial therapeutic targets of RNAi include viral infection, neurological diseases and cancer therapy. The synthesis of dsRNA displaying the desired nucleotide sequence is straightforward. However, as in the case of additional nucleic-acid-based therapeutic approaches, major technical hurdles remain to be overcome before RNAi becomes a therapeutic reality. Naked unmodified siRNAs for example display a serum half-life of less than 1 min, due to serum nuclease degradation. Approaches to improve the RNAi pharmacokinetic profile include chemical modification of the nucleotide backbone, to render it nuclease resistant, and the use of viral or non-viral vectors, to achieve safe product delivery to cells. As such, the jury remains out in terms of the development and approval of RNAi-based medicines, in the short to medium term at least. [Pg.452]

Using chemical inhibitors of upstream kinases that potentially drive trichothecene-induced MAPK activation, two putative kinases have been identified double-stranded RNA- (dsRNA)-activated protein kinase (PKR)46 and hematopoietic cell kinase (Hck).47... [Pg.295]

PKR, a widely-expressed serine/theonine protein kinase, is activated by dsRNA, interferon, and other agents.48 PKR was first described to inhibit translation via phos-... [Pg.295]

Double-stranded RNA (dsRNA) in yeast, 26 451—452 Double-stranded RNA viruses, 3 135 Double-suction pumps, 21 60, 63 Double tipping pan vacuum filter, 11 352 Double titration method, 15 145 Double vacuum-arc remelting (VAR), in titanium sponge consolidation, 24 854 Double wall nanotubes (DWNT), 26 737 Double-wall tanks, 24 296 Doubly smart block copolymers,... [Pg.288]

RNA interference (RNAi) is a cellular defense mechanism through which double stranded RNAs (dsRNAs) are processed into short lengths of small interfering RNAs (siRNAs) of 20-25 nucleotides by an enzyme called Dicer (Fig. 3.10). [Pg.81]

In eukaryotes, DNA is generally double-stranded (dsDNA) and RNA is generally single-stranded (ssRNA). Exceptions occur in certain viruses, some of which have ssDNA genomes and wime of which have dsRNA genomes.. ... [Pg.7]

With minor modification (substitution of U for T) these rules also apply to dsRNA,... [Pg.9]

FIGURE 10.10 RNAi sequence. First the vims approaches and attaches itself to the cell wall (A). The virus injects double-stranded RNA (B) into the cell cytoplasm. The dicer attacks the dsRNA, breaking it into smaller units (C and D). These smaller units are then acted on by RISC, forming single-stranded viral RNA (E), which are rendered incapable of forming their own protein by attachment to a complement contained within the cell s own single-stranded RNA (F). [Pg.324]

Naitow, H., et al. (2001). Purification, crystalhzation and preliminary X-ray analysis of L-A a dsRNA yeast virus. /. Struct. Biol. 135,1-7. [Pg.262]


See other pages where DsRNA is mentioned: [Pg.374]    [Pg.501]    [Pg.639]    [Pg.640]    [Pg.642]    [Pg.643]    [Pg.932]    [Pg.1010]    [Pg.1037]    [Pg.1091]    [Pg.1091]    [Pg.1092]    [Pg.1092]    [Pg.1093]    [Pg.1093]    [Pg.16]    [Pg.207]    [Pg.251]    [Pg.262]    [Pg.262]    [Pg.173]    [Pg.195]    [Pg.30]    [Pg.220]    [Pg.223]    [Pg.452]    [Pg.498]    [Pg.296]    [Pg.339]    [Pg.375]    [Pg.95]    [Pg.254]    [Pg.59]    [Pg.60]   
See also in sourсe #XX -- [ Pg.7 , Pg.20 ]

See also in sourсe #XX -- [ Pg.121 ]




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DsRNA-dependent protein kinase

Viral dsRNA

Virus dsRNA

Virus dsRNA containing

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