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Article

The Alphaviral Capsid Protein Inhibits IRAK1-Dependent TLR Signaling

1
Department of Microbiology and Immunology, School of Medicine, University of Louisville, Louisville, KY 40202, USA
2
Center for Predictive Medicine and Emerging Infectious Diseases, University of Louisville, Louisville, KY 40202, USA
3
Department of Medicine, Division of Nephrology and Hypertension, School of Medicine, University of Louisville, Louisville, KY 40202, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Karla Helbig 
Viruses 2021, 13(3), 377; https://doi.org/10.3390/v13030377
Received: 3 February 2021 / Revised: 24 February 2021 / Accepted: 26 February 2021 / Published: 27 February 2021
(This article belongs to the Section Animal Viruses)
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–protein 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–protein interactions of the Sindbis virus capsid protein. These efforts led to the discovery of a series of novel host–pathogen interactions, including the identification of an interaction between the alphaviral capsid protein and the host IRAK1 protein. Importantly, this capsid–IRAK1 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–IRAK1 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–protein interactions, establish the capsid–IRAK1 interaction as a common alphavirus host–pathogen interface, and delineate the molecular consequences of the capsid–IRAK1 interaction on IRAK1-dependent signaling. View Full-Text
Keywords: alphavirus; capsid; IRAK1; toll like receptors (TLR) alphavirus; capsid; IRAK1; toll like receptors (TLR)
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MDPI and ACS Style

Landers, V.D.; Wilkey, D.W.; Merchant, M.L.; Mitchell, T.C.; Sokoloski, K.J. The Alphaviral Capsid Protein Inhibits IRAK1-Dependent TLR Signaling. Viruses 2021, 13, 377. https://doi.org/10.3390/v13030377

AMA Style

Landers VD, Wilkey DW, Merchant ML, Mitchell TC, Sokoloski KJ. The Alphaviral Capsid Protein Inhibits IRAK1-Dependent TLR Signaling. Viruses. 2021; 13(3):377. https://doi.org/10.3390/v13030377

Chicago/Turabian Style

Landers, V. D.; Wilkey, Daniel W.; Merchant, Michael L.; Mitchell, Thomas C.; Sokoloski, Kevin J. 2021. "The Alphaviral Capsid Protein Inhibits IRAK1-Dependent TLR Signaling" Viruses 13, no. 3: 377. https://doi.org/10.3390/v13030377

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