Conflict in the Intracellular Lives of Endosymbionts and Viruses: A Mechanistic Look at Wolbachia-Mediated Pathogen-blocking

At the forefront of vector control efforts are strategies that leverage host-microbe associations to reduce vectorial capacity. The most promising of these efforts employs Wolbachia, a maternally transmitted endosymbiotic bacterium naturally found in 40% of insects. Wolbachia can spread through a population of insects while simultaneously inhibiting the replication of viruses within its host. Despite successes in using Wolbachia-transfected mosquitoes to limit dengue, Zika, and chikungunya transmission, the mechanisms behind pathogen-blocking have not been fully characterized. Firstly, we discuss how Wolbachia and viruses both require specific host-derived structures, compounds, and processes to initiate and maintain infection. There is significant overlap in these requirements, and infection with either microbe often manifests as cellular stress, which may be a key component of Wolbachia's anti-viral effect. Secondly, we discuss the current understanding of pathogen-blocking through this lens of cellular stress and develop a comprehensive view of how the lives of Wolbachia and viruses are fundamentally in conflict with each other. A thorough understanding of the genetic and cellular determinants of pathogen-blocking will significantly enhance the ability of vector control programs to deploy and maintain effective Wolbachia-mediated control measures.