Fig 1.
Orthoflaviviruses exploit multiple putative receptors to initiate infection.
Sankey plot highlighting the diversity of putative receptors (left) associated with orthoflavivirus infection (right) and the experimental systems from whence they were identified across diverse cellular systems (center). The highlighted flows represent the putative receptors identified in mosquito vector studies (magenta) and their corresponding orthologs (light blue) detected in insect cells and/or human cells [5–7]. The figure was generated Microsoft Excel using the SankeyArt GmbH plug-in (https://www.sankeyart.com/excel/).
Fig 2.
Multifactorial influences on mosquito midgut infection.
An illustration depicting arbovirus midgut infection barrier in Aedes aegypti mosquitoes. It is known that midgut infection is initiated through only a handful of cells, but the reasons why are unclear. Here, we highlight five poorly defined factors potentially involved in mediating orthoflavivirus infection of mosquitoes. (A) Orthoflaviviruses utilize receptor-mediated endocytosis to infect cells; however, a bona fide receptor has yet to be identified, and it is unclear if such a receptor is homogeneously expressed across the midgut epithelium. (B) The mosquito midgut contains four primary cell types and numerous subpopulations, and it is unknown whether orthoflavivirus utilize a specific cell type to initiate midgut infection. (C) sNS1 is highly conserved and has been shown to enhance viral infection in mosquitoes, but the mechanism of enhancement is unresolved. Evidence suggests that sNS1 may act as a bridging molecule facilitating interactions between extracellular virus particles and the midgut epithelium. (D, E) Wolbachia-mediated inhibition of orthoflavivirus infection of mosquitoes is well described, but it is unclear if inhibition occurs at the point of infection, during replication, or during cell-to-cell spread. Further, it is unknown if Wolbachia infection of the midgut epithelium is homogenous (D) or variable across cell types (E) and the implications of this on orthoflavivirus infection and inhibition. The image was Created in BioRender. Brackney, D. (2025) https://biorender.com/dkr7waj.