The CARD9-Associated C-Type Lectin, Mincle, Recognizes La Crosse Virus (LACV) but Plays a Limited Role in Early Antiviral Responses against LACV

João T Monteiro,Wolfgang Baumgärtner,Kathleen Schön,Tim Ebbecke,Ralph Goethe,Jürgen Ruland,Bernd Lepenies,Stefanie C Becker

doi:10.3390/v11030303

João T Monteiro, Wolfgang Baumgärtner + Show 6 more

Open Access

https://doi.org/10.3390/v11030303

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Abstract

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.

Highlights

La Crosse virus (LACV) is a mosquito-borne member of the California encephalitis group of the order Bunyavirales [1,2]
To evaluate LACV/C-type lectin receptors (CLRs) interactions, highly pure virus samples were required, since CLRs are are known to interact with glycoproteins or other glycoconjugates from damaged and necrotic known to interact with glycoproteins or other glycoconjugates from damaged and necrotic cells [16]
In order to assess the role of Macrophage-inducible Ca2+ -dependent lectin receptor (Mincle) and caspase recruitment domain family member 9 (CARD9) in LACV infection, first we evaluated if LACV

Summary

Introduction

La Crosse virus (LACV) is a mosquito-borne member of the California encephalitis group of the order Bunyavirales [1,2]. Children are more susceptible than adults to virus-mediated neurological diseases since the immune system is relatively immature at birth and during childhood [5,6]. LACV is one of the main causative agents of pediatric viral encephalitis in the USA, affecting mostly children under the age of 16 [7,8]. Viruses 2019, 11, 303 account for up to 300,000 infections/year, of which, ~70 cases/year result in a severe outcome like meningitis, encephalitis, or meningoencephalitis [3,7,9]. During natural transmission by the bite of an infected mosquito, LACV encounters dermal innate immune cells, predominantly dendritic cells (DCs), and macrophages at the site of infection [10]

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