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Results for “Double Stranded RNA Viruses”

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At least 433 records · Page 24Linked to original sources
PubMed2001

Inhibition of L-deleted foot-and-mouth disease virus replication by alpha/beta interferon involves double-stranded RNA-dependent protein kinase.

We previously demonstrated that the ability of foot-and-mouth disease virus (FMDV) to form plaques in cell culture is associated with the suppression of alpha/beta interferon (IFN-alpha/beta). In the present study, we used Escherichia coli-expressed porcine and bovine IFN-alpha or -beta individually to demonstrate that each was equally effective in inhibiting FMDV replication. The block in FMDV replication appeared to be at the level of protein translation, suggesting a role for double-stranded RNA-dependent protein kinase (PKR). In support of these findings, treatment of porcine and bovine cells with 2-aminopurine, an inhibitor of PKR, increased the yield of virus 8.8- and 11.2-fold, respectively, compared to that in untreated infected cells. In addition, results of FMDV infection in mouse embryonic fibroblast cells derived from gene knockout mice lacking the gene for RNase L(-/-) or PKR(-/-) or both indicated an important role for PKR in the inhibition of FMDV replication.

Animals↗
PubMed2006

Role of MAPK in the regulation of double-stranded RNA- and encephalomyocarditis virus-induced cyclooxygenase-2 expression by macrophages.

In response to virus infection or treatment with dsRNA, macrophages express the inducible form of cyclooxygenase-2 (COX-2) and produce proinflammatory prostaglandins. Recently, we have shown that NF-kappaB is required for encephalomyocarditis virus (EMCV)- and dsRNA-stimulated COX-2 expression in mouse macrophages. The dsRNA-dependent protein kinase R is not required for EMCV-stimulated COX-2 expression, suggesting the presence of protein kinase R-independent pathways in the regulation of this antiviral gene. In this study, the role of MAPK in the regulation of macrophage expression of cyclooxygenase-2 (COX)-2 in response to EMCV infection was examined. Treatment of mouse macrophages or RAW-264.7 cells with dsRNA or infection with EMCV stimulates the rapid activation of the MAPKs p38, JNK, and ERK. Inhibition of p38 and JNK activity results in attenuation while ERK inhibition does not modulate dsRNA- and EMCV-induced COX-2 expression and PGE2 production by macrophages. JNK and p38 appear to selectively regulate COX-2 expression, as inhibition of either kinase fails to prevent dsRNA- or EMCV-stimulated inducible NO synthase expression by macrophages. Using macrophages isolated from TLR3-deficient mice, we show that p38 and JNK activation and COX-2 expression in response to EMCV or poly(IC) does not require the presence the dsRNA receptor TLR3. These findings support a role for p38 and JNK in the selective regulation of COX-2 expression by macrophages in response to virus infection.

Animals↗
PubMed1997

Double-stranded RNA is a trigger for apoptosis in vaccinia virus-infected cells.

The vaccinia virus E3L gene codes for double-stranded RNA (dsRNA) binding proteins which can prevent activation of the dsRNA-dependent, interferon-induced protein kinase PKR. Activated PKR has been shown to induce apoptosis in HeLa cells. HeLa cells infected with vaccinia virus with the E3L gene deleted have also been shown to undergo apoptosis, whereas HeLa cells infected with wild-type vaccinia virus do not. In this report, using virus recombinants expressing mutant E3L products or alternative dsRNA binding proteins, we show that suppression of induction of apoptosis correlates with functional binding of proteins to dsRNA. Infection of HeLa cells with ts23, which leads to synthesis of increased dsRNA at restrictive temperature, induced apoptosis at restrictive but not permissive temperatures. Treatment of cells with cytosine arabinoside, which blocks the late buildup of dsRNA in vaccinia virus-infected cells, prevented induction of apoptosis by vaccinia virus with E3L deleted. Cells transfected with dsRNA in the absence of virus infection also underwent apoptosis. These results suggest that dsRNA is a trigger that can initiate a suicide response in virus-infected and perhaps uninfected cells.

Animals↗
PubMed1993

The E3L and K3L vaccinia virus gene products stimulate translation through inhibition of the double-stranded RNA-dependent protein kinase by different mechanisms.

Vaccinia virus has evolved multiple mechanisms to counteract the interferon-induced antiviral host cell response. Recently, two vaccinia virus gene products were shown to interfere with the activity of the double-stranded RNA-dependent protein kinase (PKR): the K3L gene product and the E3L gene product. We have evaluated the efficiency by which these gene products inhibit PKR and whether they act in a synergistic manner. The effects of the two vaccinia virus gene products were compared in an in vivo system in which translation of a reporter gene (dihydrofolate reductase or eukaryotic translation initiation factor 2 alpha [eIF-2 alpha]) was inhibited because of the localized activation of PKR. In this system, the E3L gene product, and to a lesser extent the K3L gene product, potentiated translation of the reporter gene and inhibited eIF-2 alpha phosphorylation. Analysis in vitro demonstrated that the E3L gene product inhibited PKR approximately 50- to 100-fold more efficiently than the K3L gene product. However, further studies demonstrated that the mechanism of action of these two inhibitors was different. Whereas the E3L inhibitor interfered with the binding of the kinase to double-stranded RNA, the K3L inhibitor did not. We propose that the K3L inhibitor acts through its homology to eIF-2 alpha to interfere with the interaction of eIF-2 alpha with PKR. The two inhibitors did not display a synergistic effect on translation or eIF-2 alpha phosphorylation. In addition, neither K3L nor E3L expression detectably altered cellular protein synthesis.

Eukaryotic Initiation Factor-2↗
PubMed2001

PACT and PKR: turning on NF-kappa B in the absence of virus.

Double-stranded RNA (dsRNA)-dependent protein kinase R (PKR) has been generally thought to be solely regulated by dsRNA, an intermediate in the replication of many viruses. However, the notion that PKR acts solely as a sensor for viral infection has been challenged by recent findings that alteration of PKR activity has effects on cellular growth and by the discovery of a virus-independent activator of PKR, a cellular protein called PACT (PKR-activating protein). The activation of the transcription factor nuclear factor kappa B (NF-kappaB) by PKR has been shown to account for the host antiviral response. We summarize the most recent findings on the molecular mechanisms leading to the activation of NF-kappaB by PKR and discuss three major unanswered questions. First, is PACT an alternative to dsRNA as a direct activator of the PKR-NF-kappaB pathway? Second, how is PACT itself activated and targeted to PKR? And third, what are the biological functions of PKR in the absence of viral infection?

Animals↗
PubMed2006

Isolation of a novel mycovirus OMIV in Pleurotus ostreatus and its detection using a triple antibody sandwich-ELISA.

A novel mycovirus was isolated from a diseased mushroom, Pleurotus ostreatus, using a purification procedure involving polyethylene glycol (PEG)-NaCl precipitation, differential centrifugation, and equilibrium centrifugation in a CsCl gradient. The virion was a 43 nm isometric virus encapsulating double-stranded RNA (dsRNA) genome of 2.1, 2.0, 1.9, and 1.7 kbp with a coat protein (CP) of 58 kDa. The new mycovirus was named Oyster Mushroom Isometric Virus (OMIV). A triple antibody sandwich-ELISA (TAS-ELISA) system was constructed to detect OMIV in the mushroom using an anti-OMIV mouse monoclonal antibody and an anti-OMIV rabbit polyclonal serum. The TAS-ELISA system was sensitive enough to allow detection of OMIV in the mushroom with the naked eye. It detected successfully virus particles from 0.6 mg of diseased tissue as well as 0.4 microg/ml purified virus preparation.

Antibodies, Viral↗
PubMed1977

Antiviral effects of double-stranded RNA from rice dwarf virus on infection of mice with western equine encephalitis virus.

A single administration (1 to 10 mg/kg) of rice dwarf virus RNA (RDV-RNA) prior to virus challenge reduced the mortality of mice infected with western equine encephalitis (WEE) virus. The protective effect of RDV-RNA was significantly higher than that of polyinosinic-polycytidylic acid. However, when these RNAs were given after virus infection, the protective effect was negligible. The titer of circulating interferon in mice reached a peak about 5 hr after injection of these RNAs and remained at this level for about 24 hr. Viremia in mice infected with a lethal dose of WEE virus was markedly suppressed by the treatment of mice with these RNAs. A pathological examination of mice treated with a lethal dose of RDV-RNA revealed marked changes including degeneration and karyorrhexis in the lymphoid tissues of the spleen.

Animals↗
PubMed2005

The birnavirus crystal structure reveals structural relationships among icosahedral viruses.

Double-stranded RNA virions are transcriptionally competent icosahedral particles that must translocate across a lipid bilayer to function within the cytoplasm of the target cell. Birnaviruses are unique among dsRNA viruses as they have a single T = 13 icosahedral shell, lacking the characteristic inner capsid observed in the others. We determined the crystal structures of the T = 1 subviral particle (260 angstroms in diameter) and of the T = 13 intact virus particle (700 angstroms in diameter) of an avian birnavirus to 3 angstroms and 7 angstroms resolution, respectively. Our results show that VP2, the only component of the virus icosahedral capsid, is homologous both to the capsid protein of positive-strand RNA viruses, like the T = 3 nodaviruses, and to the T = 13 capsid protein of members of the Reoviridae family of dsRNA viruses. Together, these results provide important insights into the multiple functions of the birnavirus capsid and reveal unexpected structural relationships among icosahedral viruses.

Amino Acid Sequence↗
PubMed1983

Tobacco mosaic virus protein synthesis is correlated with double-stranded RNA synthesis and not single-stranded RNA synthesis.

The synthesis rates of three proteins of tobacco mosaic virus (TMV), 160, 110, and 17.5 kDa, were monitored at intervals after interruption of synthesis of TMV RNA. Following inhibition of synthesis of both single-stranded and double-stranded RNAs by shifting wild type TMV to 40 degrees or ts mutant III2-35 to 35 degrees, the synthesis rates of viral proteins declined sequentially, with that of the larger proteins declining faster. When viral RNA synthesis was prevented with cordycepin, synthesis rates of the 110 and 160-kDa proteins declined rapidly, while the 17.5-kDa protein decreased more slowly. These data imply that the functional mRNA is transitory, probably nascent RNA, and that each protein is produced independently. The process of translation of viral mRNA was not temperature sensitive and occurred normally for brief periods after shift to restrictive temperatures. When single-stranded RNA synthesis was inhibited differentially from double-stranded RNA synthesis, protein synthesis was correlated with double-stranded RNA synthesis and not single-stranded RNA synthesis. Following a shift of ts mutant IV-35 to 35 degrees, a shift that immediately stopped single-stranded RNA synthesis without inhibiting double-stranded RNA synthesis, all three viral proteins continued to be produced normally. Also, after return of wild type TMV to 25 degrees after a 1-hr incubation at 40 degrees, viral protein and double-stranded RNA synthesis recovered in parallel to the normal rate after 8 hr whereas single-stranded RNA synthesis, which had been reduced more drastically, recovered more slowly after 16 hr.

Deoxyadenosines↗