2026-05-04T08:01:26Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/95272024-09-05T00:05:20Zcom_10259_4862com_10259_5086com_10259_2604col_10259_4863

Subcellular Localizations of RIG-I, TRIM25, and MAVS Complexes Sánchez-Aparicio, M. T. Ayllón Barasoain, Juan Leo-Macias, A. Wolff, T. García Sastre, Adolfo Influenza Innate immunity Microscopy Pathogen recognition receptors RIG-I Virus 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. 2024-09-04T11:23:25Z 2024-09-04T11:23:25Z 2017-01 info:eu-repo/semantics/article 0022-538X http://hdl.handle.net/10259/9527 10.1128/jvi.01155-16 1098-5514 eng Journal of Virology. 2017, V. 91, n. 2, e01155-16 https://doi.org/10.1128/jvi.01155-16 info:eu-repo/grantAgreement/NIH//1S10RR024745-01A1/US/ info:eu-repo/grantAgreement/NIAID//HHSN272201400008C/US/ info:eu-repo/grantAgreement/NIAID//U19AI117873/US/ info:eu-repo/semantics/openAccess American Society for Microbiology