2026-05-04T08:55:14Zhttps://riubu.ubu.es/oai/request

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

Sánchez-Aparicio, M. T. ea4cf178-af81-44b8-a090-cc7b002ed87e 500 Ayllón Barasoain, Juan 852 600 0000-0002-7556-8106 Leo-Macias, A. 3893ba74-5469-4a5c-9c60-252e04941dfa Wolff, T. d0391d5c-34a1-43df-a199-a292794d49a9 García Sastre, Adolfo 9de2ea8b-c019-414d-bb90-b1d51ef5bbd7 600 2024-09-04T11:23:25Z 2024-09-04T11:23:25Z 2017-01 0022-538X http://hdl.handle.net/10259/9527 10.1128/jvi.01155-16 1098-5514 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. 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.). application/pdf eng American Society for Microbiology 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/ Influenza Innate immunity Microscopy Pathogen recognition receptors RIG-I Virus Medicina Salud Microbiología Enfermedades infecciosas Medicine Health Microbiology Communicable diseases Subcellular Localizations of RIG-I, TRIM25, and MAVS Complexes info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/openAccess Journal of Virology 91 2 THUMBNAIL Aparicio-jv_2017.pdf.jpg Aparicio-jv_2017.pdf.jpg IM Thumbnail image/jpeg 3355 https://riubu.ubu.es/bitstream/10259/9527/3/Aparicio-jv_2017.pdf.jpg 0243a5a1fd12ad3c230f93478eaeb116 MD5 3 LICENSE license.txt license.txt text/plain; charset=utf-8 999 https://riubu.ubu.es/bitstream/10259/9527/2/license.txt b295bcbce42e2caabeb0c623d3860c06 MD5 2 ORIGINAL Aparicio-jv_2017.pdf Aparicio-jv_2017.pdf application/pdf 5323923 https://riubu.ubu.es/bitstream/10259/9527/1/Aparicio-jv_2017.pdf a20ad9416f42666a33460cea7760b849 MD5 1 10259/9527 oai:riubu.ubu.es:10259/9527 2024-09-05 02:05:20.345 Repositorio Institucional de la Universidad de Burgos bubrep@ubu.es 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