{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:24:17Z","timestamp":1790663057118,"version":"4.1.0"},"reference-count":121,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T00:00:00Z","timestamp":1614384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM125504"],"award-info":[{"award-number":["P20GM125504"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI153275"],"award-info":[{"award-number":["R01AI153275"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32AI132146"],"award-info":[{"award-number":["T32AI132146"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jewish Heritage Fund for Excellence","award":["Research Enhancement Grant"],"award-info":[{"award-number":["Research Enhancement Grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Alphaviruses are arthropod-borne RNA viruses which can cause either mild to severe febrile arthritis which may persist for months, or encephalitis which can lead to death or lifelong cognitive impairments. The non-assembly molecular role(s), functions, and protein\u2013protein interactions of the alphavirus capsid proteins have been largely overlooked. Here we detail the use of a BioID2 biotin ligase system to identify the protein\u2013protein interactions of the Sindbis virus capsid protein. These efforts led to the discovery of a series of novel host\u2013pathogen interactions, including the identification of an interaction between the alphaviral capsid protein and the host IRAK1 protein. Importantly, this capsid\u2013IRAK1 interaction is conserved across multiple alphavirus species, including arthritogenic alphaviruses SINV, Ross River virus, and Chikungunya virus; and encephalitic alphaviruses Eastern Equine Encephalitis virus, and Venezuelan Equine Encephalitis virus. The impact of the capsid\u2013IRAK1 interaction was evaluated using a robust set of cellular model systems, leading to the realization that the alphaviral capsid protein specifically inhibits IRAK1-dependent signaling. This inhibition represents a means by which alphaviruses may evade innate immune detection and activation prior to viral gene expression. Altogether, these data identify novel capsid protein\u2013protein interactions, establish the capsid\u2013IRAK1 interaction as a common alphavirus host\u2013pathogen interface, and delineate the molecular consequences of the capsid\u2013IRAK1 interaction on IRAK1-dependent signaling.<\/jats:p>","DOI":"10.3390\/v13030377","type":"journal-article","created":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T20:55:44Z","timestamp":1614459344000},"page":"377","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The Alphaviral Capsid Protein Inhibits IRAK1-Dependent TLR Signaling"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6586-6049","authenticated-orcid":false,"given":"V. Douglas","family":"Landers","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, University of Louisville, Louisville, KY 40202, USA"},{"name":"Center for Predictive Medicine and Emerging Infectious Diseases, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel W.","family":"Wilkey","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology and Hypertension, School of Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Merchant","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology and Hypertension, School of Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas C.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8728-2340","authenticated-orcid":false,"given":"Kevin J.","family":"Sokoloski","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, University of Louisville, Louisville, KY 40202, USA"},{"name":"Center for Predictive Medicine and Emerging Infectious Diseases, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1128\/mr.58.3.491-562.1994","article-title":"The alphaviruses: Gene expression, replication, and evolution","volume":"58","author":"Strauss","year":"1994","journal-title":"Microbiol. 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