Abstract

Several medically important flaviviruses that are transmitted by mosquitoes have been shown to bind to the C-type lectin fold that is present in either vertebrate or invertebrate proteins. While in some cases this interaction is part of a neutralizing anti-viral immune response, many reports have implicated this as critical for successful virus entry. Despite the establishment of mosquito C-type lectin domain containing proteins (CTLDcps) as known host factors in assisting the infectious process for flaviviruses, little is known about the structural characteristics of these proteins and their relationships to each other. In this report, we describe the manual annotation and structural characterization of 52 Aedes aegypti CTLDcps. Using existing RNAseq data, we establish that these genes can be subdivided into two classes: those highly conserved with expression primarily in development (embryo/early larvae) and those with no clear orthologs with expression primarily in late larvae/pupae or adults. The latter group contained all CTLDcps that are regulated by the Toll/Imd immune pathways, all known microbiome-regulating CTLDcps, and almost all CTLDcps that are implicated as flavivirus host factors in A. aegypti. Finally, we attempt to synthesize results from multiple conflicting gene expression profiling experiments in terms of how flavivirus infection changes steady-state levels of mRNA encoding CTLDcps.

Highlights

  • Important flaviviruses, such as dengue virus (DENV), Zika virus (ZIKV), West Nile encephalitis virus (WNV), Japanese encephalitis virus (JEV), and yellow fever virus (YFV) are transmitted to humans through the bite of an infected mosquito vector

  • A. aegypti is the primary vector of DENV, ZIKV, and YFV, while mosquitoes of the genus Culex, such as C. quinquefasciatus, vector WNV, and JEV

  • Of these experiments have demonstrated that the depletion of C-type lectin domain containing proteins (CTLDcps) reduces viral RNA levels, while transient overexpression increases viral RNA levels

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Summary

Introduction

Important flaviviruses, such as dengue virus (DENV), Zika virus (ZIKV), West Nile encephalitis virus (WNV), Japanese encephalitis virus (JEV), and yellow fever virus (YFV) are transmitted to humans through the bite of an infected mosquito vector. A. aegypti is the primary vector of DENV, ZIKV, and YFV, while mosquitoes of the genus Culex, such as C. quinquefasciatus, vector WNV, and JEV. In all cases, these arthropod-borne viruses (arboviruses) must escape the hostile environment of the mosquito gut and complete multiple rounds of replication in mosquito cells of the gut and body before a sufficient number of virus particles reach the salivary ducts where they can be passed on to a new vertebrate host. A family of proteins containing a C-type lectin domain (CTLD) has been implicated in binding to the glycosylated surface of flaviviruses, such as WNV, DENV, and JEV and promoting their entry (and replication) into mosquito cells [1,2,3]. Comparison of these proteins with both Drosophila and A. gambiae

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