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 Wolbachia-mediated extent of Wolbachia-induced pathogen enhancement, and the mechanism(s) leading to this phenotype enhancement of several arboviral human pathogens in the 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 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 he 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.

Public Health Relevance

Infection with Wolbachia bacteria commonly makes vector insects refractory to pathogen transmission. However, Wolbachia infection can at times increase pathogen transmission by vector insects. We have discovered that Wolbachia can enhance infection of multiple arboviruses in Culex tarsalis mosquitoes. In this research, we will quantify how common Wolbachia-?based pathogen enhancement is in mosquitoes and determine the mechanism(s) responsible for WNV enhancement. These data will allow us to estimate 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI116636-01A1
Application #
9107036
Study Section
Vector Biology Study Section (VB)
Program Officer
Costero-Saint Denis, Adriana
Project Start
2016-02-15
Project End
2021-01-31
Budget Start
2016-02-15
Budget End
2017-01-31
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Zoology
Type
Earth Sciences/Resources
DUNS #
003403953
City
University Park
State
PA
Country
United States
Zip Code
16802
Dodson, Brittany L; Andrews, Elizabeth S; Turell, Michael J et al. (2017) Wolbachia effects on Rift Valley fever virus infection in Culex tarsalis mosquitoes. PLoS Negl Trop Dis 11:e0006050
Macias, Vanessa M; Ohm, Johanna R; Rasgon, Jason L (2017) Gene Drive for Mosquito Control: Where Did It Come from and Where Are We Headed? Int J Environ Res Public Health 14:
Dodson, Brittany L; Rasgon, Jason L (2017) Vector competence of Anopheles and Culex mosquitoes for Zika virus. PeerJ 5:e3096
Tsujimoto, Hitoshi; Sakamoto, Joyce M; Rasgon, Jason L (2017) Functional characterization of Aquaporin-like genes in the human bed bug Cimex lectularius. Sci Rep 7:3214
Hughes, Grant L; Raygoza Garay, Juan Antonio; Koundal, Vikas et al. (2016) Genome Sequences of Staphylococcus hominis Strains ShAs1, ShAs2, and ShAs3, Isolated from the Asian Malaria Mosquito Anopheles stephensi. Genome Announc 4:
Pujhari, Sujit; Rasgon, Jason L; Zakhartchouk, Alexander N (2016) Anti-apoptosis in porcine respiratory and reproductive syndrome virus. Virulence 7:610-1
Barik, Tapan K; Suzuki, Yasutsugu; Rasgon, Jason L (2016) Factors influencing infection and transmission of Anopheles gambiae densovirus (AgDNV) in mosquitoes. PeerJ 4:e2691
Lindsey, Amelia R I; Bordenstein, Seth R; Newton, Irene L G et al. (2016) Wolbachia pipientis should not be split into multiple species: A response to Ramírez-Puebla et al., ""Species in Wolbachia? Proposal for the designation of 'Candidatus Wolbachia bourtzisii', 'Candidatus Wolbachia onchocercicola', 'Candidatus Wolbachia bla Syst Appl Microbiol 39:220-222
Raygoza Garay, Juan Antonio; Hughes, Grant L; Koundal, Vikas et al. (2016) Genome Sequence of Elizabethkingia anophelis Strain EaAs1, Isolated from the Asian Malaria Mosquito Anopheles stephensi. Genome Announc 4:
Liu, Kun; Tsujimoto, Hitoshi; Huang, Yuzheng et al. (2016) Aquaglyceroporin function in the malaria mosquito Anopheles gambiae. Biol Cell 108:294-305

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