title: A sodium channel variant in Aedes aegypti as a candidate pathogen sensor for viral-associated molecular patterns.
abstract: Recent work demonstrated that a splice variant of a human macrophage voltage-gated sodium channel expressed on endosomes acts as an intracellular sensor for dsRNA, a viral-associated molecular pattern. Here our goal was to identify a candidate gene in a clinically relevant invertebrate model with related cellular and pattern recognition properties. The para gene in drosophila and other insects encodes voltage-gated sodium channels with similar electrophysiological properties to those found in vertebrate excitable membranes. A database search revealed that the AAEL006019 gene in Aedes aegypti, the yellow fever mosquito, encodes a voltage-gated sodium channel that is distinct from genes that encode para-like sodium channels. As compared to para-like channels, the protein products from this gene have deletions in the N-terminus and in the DII-DIII linker region. When over-expressed in an Aedes aegypti cell line, CCL-125, the AAEL006019 channel demonstrated cytoplasmic expression on vesicular-like organelles. Electrophysiologic analysis revealed that the channel mediates small inward currents that are enhanced by synthetic mimics of viral-derived ssRNA, R848 and ORN02, but not the dsRNA mimic, poly I:C. R848 treatment of CCL-125 cells that express high levels of the channels led to increased expression of RelA and Ago2, two mediators of insect innate immunity. These results suggest that the AAEL006019 channel acts as an intracellular pathogen sensor for ssRNA molecular patterns.
authors.affiliation: Departments of Neurology, Pathology and Program in Cellular and Molecular Pathology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Cara
authors.initials: C
authors.lastname: Lee
authors.affiliation: Departments of Neurology, Pathology and Program in Cellular and Molecular Pathology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Alexis
authors.initials: A
authors.lastname: Jones
authors.affiliation: Departments of Neurology, Pathology and Program in Cellular and Molecular Pathology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Kainz
authors.affiliation: Departments of Neurology, Pathology and Program in Cellular and Molecular Pathology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Faatima
authors.initials: F
authors.lastname: Khan
authors.affiliation: Departments of Neurology, Pathology and Program in Cellular and Molecular Pathology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI, USA. Electronic address: mcar1@uic.edu.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Carrithers
mesh_terms: D000330:Aedes / Q000378:metabolism*; D000818:Animals; D015374:Biosensing Techniques; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating; D015222:Sodium Channels / Q000378:metabolism*
chemical_list: D015222:Sodium Channels
keywords: Imidazolquinilone; Para; RelA; Yellow fever mosquito; ssRNA