Wolbachia enhances insect‐specific flavivirus infection in Aedes aegypti mosquitoes

Abstract

Mosquitoes transmit a diverse group of human flaviviruses including West Nile, dengue, yellow fever, and Zika viruses. Mosquitoes are also naturally infected with insect‐specific flaviviruses (ISFs), a subgroup of the family not capable of infecting vertebrates. Although ISFs are not medically important, they are capable of altering the mosquito's susceptibility to flaviviruses and may alter host fitness. Wolbachia is an endosymbiotic bacterium of insects that when present in mosquitoes limits the replication of co‐infecting pathogens, including flaviviruses. Artificially created Wolbachia‐infected Aedes aegypti mosquitoes are being released into the wild in a series of trials around the globe with the hope of interrupting dengue and Zika virus transmission from mosquitoes to humans. Our work investigated the effect of Wolbachia on ISF infection in wild‐caught Ae. aegypti mosquitoes from field release zones. All field mosquitoes were screened for the presence of ISFs using general degenerate flavivirus primers and their PCR amplicons sequenced. ISFs were found to be common and widely distributed in Ae. aegypti populations. Field mosquitoes consistently had higher ISF infection rates and viral loads compared to laboratory colony material indicating that environmental conditions may modulate ISF infection in Ae. aegypti. Surprisingly, higher ISF infection rates and loads were found in Wolbachia‐infected mosquitoes compared to the Wolbachia‐free mosquitoes. Our findings demonstrate that the symbiont is capable of manipulating the mosquito virome and that Wolbachia‐mediated viral inhibition is not universal for flaviviruses. This may have implications for the Wolbachia‐based DENV control strategy if ISFs confer fitness effects or alter mosquito susceptibility to other flaviviruses.

Contrasting Patterns of Virus Protection and Functional Incompatibility Genes in Two ConspecificWolbachiaStrains fromDrosophila pandora

“…4). Although unanticipated, these results reflect the high degree of variability that exists across the Wolbachia phylogeny in terms of the interactions of this symbiont with other host viruses (33,64,65,81,(83)(84)(85). These effects on survival were shown not to be related to changes in viral accumulation (Fig.…”

Aedes Anphevirus: an Insect-Specific Virus Distributed Worldwide in Aedes aegypti Mosquitoes That Has Complex Interplays with Wolbachia and Dengue Virus Infection in Cells

“…Perhaps the combination of protection of the RNA nucleocapsid genome or genome segments when released in the cytoplasm or activity of the RdRp aids in evasion of host immune response enhanced by Wolbachia or Wolbachia effector molecules (92). However, a recent study suggested increases in infection of A. aegypti mosquitoes by insect-specific flaviviruses when they harbor the Wolbachia wMel strain (93).…”

Development of a Confinable Gene-Drive System in the Human Disease Vector,Aedes aegypti

“…In addition to IIT, Wolbachia has also been used for population replacement in various locations (8)(9)(10), as certain strains can spread to fixation while greatly reducing the vector's susceptibility to dengue virus (11). However, the literature suggests the effectiveness of different Wolbachia strains varies so far as to even enhance vector competence in some contexts, which may lead to a reevaluation of this technique (12)(13)(14)(15)(16)(17)(18). Therefore, there has been renewed interest in developing novel species-specific and cost-effective genetic technologies that provide long-lasting disease reduction with limited effort.…”