Aedes aegypti ML and Niemann-Pick type C family members are agonists of dengue virus infection

Abstract

Upon exposure to dengue virus, the Aedes aegypti mosquito vector mounts an anti-viral immune defense by activating the Toll, JAK/STAT, and RNAi pathways, thereby limiting infection. While these pathways and several other factors have been identified as dengue virus antagonists, our knowledge of factors that facilitate dengue virus infection is limited. Previous dengue virus infection-responsive transcriptome analyses have revealed an increased mRNA abundance of members of the myeloid differentiation 2-related lipid recognition protein (ML) and the Niemann Pick-type C1 (NPC1) families upon dengue virus infection. These genes encode lipid-binding proteins that have been shown to play a role in host-pathogen interactions in other organisms. RNAi-mediated gene silencing of a ML and a NPC1 gene family member in both laboratory strain and field-derived Ae. aegypti mosquitoes resulted in significantly elevated resistance to dengue virus in mosquito midguts, suggesting that these genes play roles as dengue virus agonists. In addition to their possible roles in virus cell entry and replication, gene expression analyses suggested that ML and NPC1 family members also facilitate viral infection by modulating the mosquito’s immune competence. Our study suggests that the dengue virus influences the expression of these genes to facilitate its infection of the mosquito host.

Engineered Aedes aegypti JAK/STAT Pathway-Mediated Immunity to Dengue Virus

“…Here we confirm, for the first time, a role for SCP2 as a DENV host factor in vivo . Taken together with our transcriptomic data, which revealed regulation of lipid transport processes in both transgenic lines, and with previous studies [41,42], these results emphasize important roles for lipid homeostasis during DENV infection in Ae . aegypti .…”

“…JAK/STAT activation resulted in the broad induction of numerous transcripts encoding immune recognition and effector molecules, including several that have previously been shown to restrict DENV. In addition, functional pathway analyses revealed that digestion- and lipid transport-related transcripts were differentially regulated in transgenic mosquitoes; these processes have previously been shown to impact DENV replication [41,42,57]. Finally, JAK/STAT activation also down-regulated transcript abundances of several genes that have known or potential roles as DENV host factors.…”

“…Lipid metabolism is known to be influenced by the JAK/STAT pathway [36], and also plays important roles in the replication of DENV, an enveloped virus. DENV is thought to facilitate its own replication by altering the expression of lipid-binding proteins and enzymes involved in lipid biosynthesis, such as fatty acid synthases and Niemann-Pick type C protein family members [41,42]. …”

Characterization of the Rel2-regulated transcriptome and proteome of Anopheles stephensi identifies new anti-Plasmodium factors

“…NPC2 also plays an important role in dengue resistance of Ae. aegypti mosquitoes and may play a role in a variety of infection systems (Jupatanakul et al ., 2013). A2MRAP (ASTE011001/AGAP003521) is a protein associated with the receptor for alpha-2-macroglobulins.…”

Diversity of Cultivable Midgut Microbiota at Different Stages of the Asian Tiger Mosquito, Aedes albopictus from Tezpur, India

“…A number of bacterial species isolated from the mosquito midguts have also been utilized for manipulating their midgut microbiota (paratransgenesis), to modulate the vector competency of the mosquitoes, as a potent strategy for vector management [13–15]. Interestingly, the midgut microbial flora is dynamic and the diversity changes with the development of the vectors, in addition to other factors such as species, sex, life-stage, feeding behavior and geographical origin [16–22]. As a conventional assumption, midgut bacterial population is thought to be acquired from the environment, in which the said species develops.…”