Exploring the Protein-Protein Interactions, Traffic, and Functions of the Dengue Virus Non-structural 1 (NS1) Protein in the Vector Mosquito

Dengue is the most important viral disease transmitted to humans by mosquitoes. Aedes aegypti and Aedes albopictus are the two species of mosquito mainly responsible for the urban cycle of dengue. Dengue is caused by the dengue virus, classified in the Orthoflavivirus genus, within the family Flaviviridae. The dengue virus RNA genome encodes for 10 proteins: three structural (C, prM, and E) and 7 non-structural proteins (NS1–NS5). The NS1 protein is a multifunctional, conserved glycoprotein that is present only in vector-borne flaviviruses. Cytoplasmic NS1 is a homodimer that participates in viral replication and morphogenesis. In addition, NS1 in association with lipids, is secreted as hexameric and tetrameric forms; the extracellular, soluble forms of NS1 have been implicated in dengue pathogenesis through several mechanisms. However, much less is known about NS1 functions in the mosquito cells than in the vertebrate cells—a gap that needs to be closed toward better dengue control measurements. Evidence gathered by us and others suggest that relevant differences in NS1 traffic and functions exist between dengue virus-infected mammalian and mosquito cells. In this chapter, we discuss such evidence and hypothesize about the implications of these differences for the biology of dengue virus.