The RIG-I-like receptor LGP2 inhibits Dicer-dependent processing of long double-stranded RNA and blocks RNA interference in mammalian cells
In vertebrates, the presence of viral RNA in the cytosol is sensed by members of the RIG-I-like receptor (RLR) family, which signal to induce production of type I interferons (IFN). These key antiviral cytokines act in a paracrine and autocrine manner to induce hundreds of interferon-stimulated genes (ISGs), whose protein products restrict viral entry, replication and budding. ISGs include the RLRs themselves: RIG-I, MDA5 and, the least-studied family member, LGP2. In contrast, the IFN system is absent in plants and invertebrates, which defend themselves from viral intruders using RNA interference (RNAi). In RNAi, the endoribonuclease Dicer cleaves virus-derived double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs) that target complementary viral RNA for cleavage. Interestingly, the RNAi machinery is conserved in mammals, and we have recently demonstrated that it is able to participate in mammalian antiviral defence in conditions in which the IFN system is suppressed. In contrast, when the IFN system is active, one or more ISGs act to mask or suppress antiviral RNAi. Here, we demonstrate that LGP2 constitutes one of the ISGs that can inhibit antiviral RNAi in mammals. We show that LGP2 associates with Dicer and inhibits cleavage of dsRNA into siRNAs both in vitro and in cells. Further, we show that in differentiated cells lacking components of the IFN response, ectopic expression of LGP2 interferes with RNAi-dependent suppression of gene expression. Conversely...
Abstract Laryngeal trauma from prolonged endotracheal intubation occurs in patients of all ages. Most changes are superficial and heal quickly. Injuries that are found consistently during intubation include nonspecific changes, edema, granulation tissue, ulceration, and othermiscellaneous injuries. In thispapersignificant, severe, and lasting trauma of the larynx has been classified on thebasis of theknown factors in pathogenesis, observations made atendoscopy, and photographic documentation. This classification has required introduction of new descriptive terminology: "tongues of granulation tissue," &q...
PMID: 30012011 [PubMed - in process]
PMID: 30012010 [PubMed - in process]
PMID: 30012009 [PubMed - in process]
The FDA has approved the first protease inhibitor-based single-tablet regimen for the treatment of HIV-1 infection in treatment-naive and certain virologically suppressed adult patients.FDA Approvals
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