Infections of Aedes Mosquito Cells by Wolbachia Strains wAu and wMelpop Modulate Host Cellular Transcriptomes Differently and Suppress Dengue Viral Replication

Dengue virus serotypes 1-4 (DENV1-4) have spread through tropical and subtropical countries, causing endemic and epidemic diseases. Recently, a novel field approach using the <i>Wolbachia</i> symbiont was proposed to suppress DENV transmission via the mosquito vectors <i>Aedes aegypti</i> and <i>Aedes albopictus</i>. Previously, we showed that a <i>Wolbachia</i> strain, <i>w</i>MelPop, suppresses DENV2 replication in the C6/36 <i>albopictus</i> cell line, with the mutant DENV2 appearing and replacing the wild type DENV2. In this study, we expanded the analysis to include replications of all DENV serotypes 1-4, effects of <i>w</i>Au <i>Wolbachia</i> in C6/36 cells, and <i>w</i>MelPop-influences on the Aag2 <i>aegypti</i> cell line. It was revealed that both <i>w</i>Au <i>and w</i>MelPop reduce all DENV infectious titers without dominant appearances of the mutant viruses, despite varied effects on the viral copy numbers. The host transcriptomic profiles by RNA-seq were also variously altered by <i>w</i>Au and <i>w</i>MelPop (ranging from 10 to 30%, Log₂FC > 2 or <-2, <i>p</i> < 0.05). Those transcripts were not further altered by DENV infection. In contrast, abundant transcriptomic alterations by DENV infection in naïve C6/36 and Aag2 cells were blocked by either <i>w</i>Au <i>or w</i>MelPop. These results indicate that <i>Wolbachia</i> prevents host cellular transcriptomic alterations which are induced by DENV infection, affecting the cellular homeostasis necessary for DENV replication.