Wolbachia effects on C6/36 and Aag2 cells in response to dengue virus infections

Dengue virus serotype 1-4 (DENV1-4) are spread through tropical and subtropical countries, causing endemic and epidemic diseases. Recently, a novel field approach using the Wolbachia symbiont has been challenged to suppress DENV transmission by the mosquito vectors, Aedes aegypti and Aedes albopictus. Previously, we showed that a Wolbachia strain, wMelPop suppresses DENV2 replication in the C6/36 albopictus cell line, while the mutant viruses appeared and replaced the viral population, resulting in the loss of the viral replication ability in mammalian cells. In this study, we expanded the analysis toward replications of all DENV serotypes, effects of wAu Wolbachia in C6/36 cells and wMelPop-influences on Aag2 aegypti cell line. It was revealed that both wAu and wMelPop reduce all DENV infectious titers without dominant appearances of the mutant viruses, despite varied effects on viral copy numbers. Host transcriptomic profiles by RNA-seq were also variously altered by wAu and wMelPop (ranging from 10 to 30%, Log2FC > 2 or < -2, P < 0.05). The commonly or differently altered transcripts among samples of different Wolbachia species, densities or host mosquito species were varied, while these transcripts were not further altered by DENV2 infection. In contrast, abundant transcriptomic alterations by DENV2 infection in naive C6/36 and Aag2 cells were blocked by either wAu or wMelPop. These results indicate that the Wolbachia prevents host cellular transcriptomic alterations which are induced by DENV infection, affecting cellular homeostasis necessary for DENV replication.