RT info:eu-repo/semantics/article
T1 Subcellular Localizations of RIG-I, TRIM25, and MAVS Complexes
A1 Sánchez-Aparicio, M. T.
A1 Ayllón Barasoain, Juan
A1 Leo-Macias, A.
A1 Wolff, T.
A1 García Sastre, Adolfo
K1 Influenza
K1 Innate immunity
K1 Microscopy
K1 Pathogen recognition receptors
K1 RIG-I
K1 Virus
K1 Medicina
K1 Medicine
K1 Salud
K1 Health
K1 Microbiología
K1 Microbiology
K1 Enfermedades infecciosas
K1 Communicable diseases
AB The retinoic acid-inducible gene 1 (RIG-I) signaling pathway is essential for the recognition of viruses and the initiation of host interferon (IFN)-mediated antiviral responses. Once activated, RIG-I interacts with polyubiquitin chains generated by TRIM25 and binds mitochondrial antiviral signaling protein (MAVS), leading to the production of type I IFN. We now show specific interactions among these key partners in the RLR pathway through the use of bimolecular fluorescence complementation (BiFC) and super-resolution microscopy. Dimers of RIG-I, TRIM25, and MAVS localize into different compartments. Upon activation, we show that TRIM25 is redistributed into cytoplasmic dots associated with stress granules, while RIG-I associates with TRIM25/stress granules and with mitochondrial MAVS. In addition, MAVS competes with TRIM25 for RIG-I binding, and this suggests that upon TRIM25-mediated activation of RIG-I, RIG-I moves away from TRIM25 to interact with MAVS at the mitochondria. For the first time, the distribution of these three proteins was analyzed at the same time in virus-infected cells. We also investigated how specific viral proteins modify some of the protein complexes in the pathway. The protease NS3/4A from hepatitis C virus redistributes the complexes RIG-I/MAVS and MAVS/MAVS but not RIG-I/TRIM25. In contrast, the influenza A virus NS1 protein interacts with RIG-I and TRIM25 in specific areas in the cell cytoplasm and inhibits the formation of TRIM25 homocomplexes but not the formation of RIG-I/TRIM25 heterocomplexes, preventing the formation of RIG-I/MAVS complexes. Thus, we have localized spatially in the cell different complexes formed between RIG-I, TRIM25, and MAVS, in the presence or absence of two viral IFN antagonistic proteins.
PB American Society for Microbiology
SN 0022-538X
YR 2017
FD 2017-01
LK http://hdl.handle.net/10259/9527
UL http://hdl.handle.net/10259/9527
LA eng
NO We thank Peter Lichter (Heidelberg, Germany) for the BiFC plasmids and LuisMartinez-Sobrido for the HA-NS3/4A plasmids. We also acknowledge the help of theMicroscopy Shared Resource Facility at the Icahn School of Medicine at Mount Sinai,supported with funding from an NIH Shared Instrumentation Grant (1S10RR024745-01A1).This study was partly supported by the Center for Research on Influenza Pathogen-esis, the National Institute of Allergy and Infectious Disease (NIAID)-funded Center ofExcellence for Influenza Research and Surveillance (contract HHSN272201400008C), andby NIAID grant U19AI117873 (to A.G.-S.).
DS Repositorio Institucional de la Universidad de Burgos
RD 23-nov-2024