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Rigid inflatable gastrostomy (RIG) tubes are widely used in contemporary clinical practice for a variety of indications. Insertion of RIG tubes is associated with a high technical success rate and low incidence of mortality. In this case report, a procedural pitfall associated with intraperitoneal-extragastric malposition is described. Rigorous assessment of abdominal radiographs, as well as aw...
The retinoic acid-inducible gene I product (RIG-I) is a cellular sensor of RNA virus infection that regulates the cellular beta interferon (IFN-beta) response. The nucleoproteins (NP) of arenaviruses are reported to antagonize the IFN response by inhibiting interferon regulatory factor 3 (IRF-3). Here, we demonstrate that the Z proteins of four New World (NW) arenaviruses, Guanarito virus (GTOV...
Antiviral response pathways induce interferon by higher-order assembly of signaling complexes called signalosomes. Assembly of the RIG-I signalosome is regulated by K63-linked polyubiquitin chains, which are synthesized by the E3 ubiquitin ligase, TRIM25. We have previously shown that the TRIM25 coiled-coil domain is a stable, antiparallel dimer that positions two catalytic RING domains on oppo...
The cytosolic pathogen sensor RIG-I is activated by RNAs with exposed 5'-triphosphate (5'-ppp) and terminal double-stranded structures, such as those that are generated during viral infection. RIG-I has been shown to translocate on dsRNA in an ATP-dependent manner. However, the precise role of the ATPase activity in RIG-I activation remains unclear. Using in vitro-transcribed Sendai virus defec...
Viral RNA is sensed by TLR 7 and 8 or by the RNA helicases LGP2, MDA5 and RIG-I to trigger antiviral responses. Much less is known about sensors for DNA. Here we identify a novel DNA sensing pathway involving RNA polymerase III and RIG-I. AT-rich dsDNA serve as a template for RNA polymerase III, which is transcribed into dsRNA harboring a 5′ triphosphate moiety which signals via RIG-I to activa...
UNLABELLED RIG-I is a cytosolic sensor critically involved in the activation of the innate immune response to RNA virus infection. In the present study, we evaluated the inhibitory effect of a RIG-I agonist on the replication of two emerging arthropod-borne viral pathogens, dengue virus (DENV) and chikungunya virus (CHIKV), for which no therapeutic options currently exist. We demonstrate that w...
I.1. Physical motivation. From [St]: consider a function T (x) as representing the value of a physical variable at a particular point x in space. Is this a realistic thing to do? What can you measure? Suppose T (x) represents temperature at a point x in a room. You can measure the temperature with a thermometer, placing the bulb at the point x. Unlike the point, the bulb has nonzero size, so wh...
UNLABELLED Pattern recognition receptors (PRR) sense certain molecular patterns uniquely expressed by pathogens. Retinoic-acid-inducible gene I (RIG-I) is a cytosolic PRR that senses viral nucleic acids and induces innate immune activation and secretion of type I interferons (IFNs). Here, using influenza vaccine antigens, we investigated the consequences of activating the RIG-I pathway for anti...
The innate immune sensor RIG-I responds to infection by binding to viral double-stranded RNA (dsRNA). In this issue of Cell, Kowalinski et al. (2011) and Luo et al. (2011) reveal the structure of RIG-I, and in combination with functional analyses, they show how RIG-I recognizes viral RNA to initiate signaling and a type I interferon response.
Cytoplasmic viral RNAs with 5' triphosphates (5'ppp) are detected by the RNA helicase RIG-I, initiating downstream signaling and alpha/beta interferon (IFN-alpha/beta) expression that establish an antiviral state. We demonstrate here that the hepatitis C virus (HCV) 3' untranslated region (UTR) RNA has greater activity as an immune stimulator than several flavivirus UTR RNAs. We confirmed that ...
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