Aedes aegypti transmits one of the most significant mosquito-borne viruses, dengue virus (DENV). The absence of effective
vaccines and clinical treatments and the emergence of insecticide resistance in A. aegypti necessitate novel vector control strategies. A new approach uses the endosymbiotic bacterium Wolbachia pipientis to reduce the spread of arboviruses. However, the Wolbachia-mediated
antiviral mechanism is not well understood. To shed light on this mechanism, we investigated an unexplored aspect of Wolbachia-virus-mosquito interaction. We used
RNA sequencing to examine the transcriptional response of Wolbachia to DENV
infection in A. aegypti Aag2 cells transinfected with the wAlbB strain of Wolbachia. Our results suggest that genes encoding an
endoribonuclease (
RNase HI), a regulator of sigma 70-dependent gene transcription (
6S RNA), essential cellular, transmembrane, and stress response functions and primary type I and IV secretion systems were upregulated, while a number of transport and
binding proteins of Wolbachia, ribosome structure, and
elongation factor-associated genes were downregulated due to DENV
infection. Furthermore, bacterial
retrotransposon, transposable, and phage-related elements were found among the up- and downregulated genes. We show that Wolbachia elicits a transcriptional response to
virus infection and identify differentially expressed Wolbachia genes mostly at the early stages of
virus infection. These findings highlight Wolbachia's ability to alter its gene expression in response to DENV
infection of the host cell. IMPORTANCE Aedes aegypti is a vector of several pathogenic viruses, including
dengue, Zika, chikungunya, and
yellow fever viruses, which are of importance to human health. Wolbachia is an endosymbiotic bacterium currently used in transinfected mosquitoes to suppress replication and transmission of dengue viruses. However, the mechanism of Wolbachia-mediated virus inhibition is not fully understood. While several studies have shown mosquitoes' transcriptional responses to dengue virus
infection, none have investigated these responses in Wolbachia, which may provide clues to the inhibition mechanism. Our results suggest changes in the expression of a number of functionally important Wolbachia genes upon dengue virus
infection, including those involved in stress responses, providing insights into the endosymbiont's reaction to
virus infection.