Stiftung Tierärztliche Hochschule Hannover (TiHo)

The CARD9-associated C-type lectin, mincle, recognizes La Crosse virus (LACV) but plays a limited role in early antiviral responses against LACV

Monteiro, João ORCID; Schön, Kathleen; Ebbecke, Tim; Goethe, Ralph GND; Ruland, Jürgen; Baumgärtner, Wolfgang GND; Becker, Stefanie GND; Lepenies, Bernd GND

La Crosse virus (LACV) is a mosquito-transmitted arbovirus and the main cause of virus-mediated neurological diseases in children. To date, little is known about the role of C-type lectin receptors (CLRs)-an important class of pattern recognition receptors-in LACV recognition. DC-SIGN remains the only well-described CLR that recognizes LACV. In this study, we investigated the role of additional CLR/LACV interactions. To this end, we applied a flow-through chromatography method for the purification of LACV to perform an unbiased high-throughput screening of LACV with a CLR-hFc fusion protein library. Interestingly, the CARD9-associated CLRs Mincle, Dectin-1, and Dectin-2 were identified to strongly interact with LACV. Since CARD9 is a common adaptor protein for signaling via Mincle, Dectin-1, and Dectin-2, we performed LACV infection of Mincle-/- and CARD9-/- DCs. Mincle-/- and CARD9-/- DCs produced less amounts of proinflammatory cytokines, namely IL-6 and TNF-α, albeit no reduction of the LACV titer was observed. Together, novel CLR/LACV interactions were identified; however, the Mincle/CARD9 axis plays a limited role in early antiviral responses against LACV.


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