Wolbachia-induced enhancement of human arboviral pathogens

Project: Research project

Description

? DESCRIPTION (provided by applicant): Efforts to control vector-borne pathogens have been hindered by evolution of insecticide resistance and failing drug therapies. To improve the sustainability and efficacy of control efforts, alternative vector control strategies are being considered. Infection with the maternally-inherited endosymbiont Wolbachia pipientis has been demonstrated to inhibit viruses and parasites in vector arthropods. Wolbachia-infected mosquitoes are currently being released into nature to control human disease. However, a worrying trend is emerging whereby Wolbachia infections enhance rather than suppress pathogens in insect vectors. We have now demonstrated for the first time Wolbachia-mediated enhancement of a human pathogen (West Nile virus) in a mosquito vector (Culex tarsalis); a sobering reminder that the pathogen inhibitory effects resulting from Wolbachia infection in some insects cannot and should not be generalized across vector-pathogen systems. Understanding the general extent of Wolbachia-induced pathogen enhancement, and the mechanism(s) leading to this phenotype are critical for estimating how likely Wolbachia-based control strategies are to fail or make things worse, for identifying potential points where Wolbachia-based control is likely to break down in the field, and for planning risk mitigation strategies in the case of unforeseen harmful outcomes. In this research, we will investigate the hypothesis that Wolbachia-induced modulation of the mosquito hologenome can lead to increased arbovirus infection/transmission in some vector-pathogen systems of human importance. This hypothesis will be examined in the following three Specific Aims: (1) Determine the generality of Wolbachia-induced arbovirus enhancement in multiple mosquito-pathogen systems; (2) Determine the role of Wolbachia-microbiome interactions in mediating WNV enhancement in Cx. tarsalis; (3) Determine the role of Wolbachia- induced modulation of mosquito gene transcription in mediating WNV enhancement in Cx. tarsalis.
StatusActive
Effective start/end date3/1/151/31/21

Funding

  • National Institutes of Health: $381,971.00
  • National Institutes of Health: $382,394.00
  • National Institutes of Health: $382,802.00
  • National Institutes of Health: $368,376.00
  • National Institutes of Health: $351,262.00

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Wolbachia
Culicidae
Arbovirus Infections
Arthropod Vectors
Infection
Insect Vectors
Insecticide Resistance
Arboviruses
Culex
Infectious Disease Transmission
Microbiota
Insects