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Abstract

Alphaviruses are arthropod-borne positive-sense RNA viruses that have the capacity to cause large scale outbreaks of severe disease. As of now, there are no effective therapeutic strategies with which alphaviral disease may be treated. Thus, there is a need for research that defines the mechanism(s) by which the alphaviruses establish infection and cause pathogenesis. Our previous work identified non-assembly interactions between the SINV Capsid protein and the viral genomic RNA that were important for viral RNA stabilization early during infection. These efforts led us to evaluate the Protein:Protein interactions of the SINV Capsid protein using the BioID2 discovery approach to define the mechanism of action underlying the SINV Capsid-mediated genome stability.

To our surprise, these efforts indicated that the SINV CP protein interacts with the host IRAK1 protein in tissue culture models of infection. To validate the interface we utilized a Bimolecular Fluorescence Complementation approach to confirm the SINV Capsid-IRAK1 interaction. After confirming the novel Capsid Protein:Protein interaction we hypothesized that the SINV Capsid protein may interfere with IRAK1-dependent signaling during infection. To this end, we assessed the dose-responsiveness of several IRAK1-dependent signaling pathways, including TLRs 4 and 7 in the presence of the SINV Capsid protein. We found that the TLR-agonist response, was significantly decreased in the presence of the SINV Capsid protein. Collectively, these data are highly suggestive that the SINV Capsid protein interferes with TLR signaling during viral infection contributing to the evasion of the host innate immune response.

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/content/journal/acmi/10.1099/acmi.ac2020.po0331
2020-07-10
2020-12-01
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http://instance.metastore.ingenta.com/content/journal/acmi/10.1099/acmi.ac2020.po0331
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