Mosquitoes Culex pipiens is a major vector species for Japanese encephalitis and filariasis in China, and it is an important vector of West Nile Virus in the USA. Vector control is an important means of mosquito-borne disease prevention and management. Pyrethroid insecticide is currently being promoted worldwide for disease vector control because of their high efficacy, rapid rate of knockdown, and low mammalian toxicity. Due to wide- spread and improper use of insecticides, resistance to pyrethroids is very prevalent in Cx. pipiens mosquito species in China. The long-term goal of this research is to elucidate the genetic and molecular mechanisms of pyrethroid resistance in Cx. pipiens mosquitoes, and to develop more accurate and cost-effective resistance detection methods that are applicable to field samples. During the past three-year granting period, we have established deltamethrin resistant strains of Cx. pipiens, characterized novel genes associated with deltamethrin resistance in Cx. pipiens, developed PCR-based knockdown resistance (kdr) mutation detection methods and conducted quantitative trait loci mapping for pyrethroid resistance. Because the classic genetic mapping study in our previous studies cannot identify genetic transcripts differentially regulated between susceptible and resistant individuals, this renewal application will use high-throughput transcriptome analysis and population genetic approaches to determine the relationship between pyrethroid resistance at organismal level and transcription activity and gene nucleotide polymorphisms at molecular level. Here we focus on insecticide resistance at the organism level because mosquitoes may possess compensatory mechanisms under the selection by insecticides. Studying individual genes in cell lines will not reveal resistance at the organismal level because it ignores gene-gene and gene-environment interactions.
The specific aims are: 1) to identify the major candidate genes for resistance to deltamethrin in Cx. pipiens using transcriptome analysis, 2) to determine the function of the candidate genes in pyrethroid resistance;and 3) to establish association between pyrethroid resistance at organismal level and gene polymorphisms and transcription activity at molecular level. We anticipate that this research will significantly enhance our understanding of resistance to pyrethroid insecticides in Cx. pipiens mosquitoes. The knowledge from this application will greatly facilitate the development of new resistance diagnostic methods for this important disease vector in China and the world.

Public Health Relevance

Culex pipiens is a major vector species for Japanese encephalitis and filariasis in China, and it is an important vector of West Nile Virus in the USA. Insecticide- based mosquito control is an important method, but Insecticide resistance represents a major obstacle in the struggle against vector-borne disease. This project will better understand the genetic mechanisms of resistance to pyrethroid insecticide in Cx. pipiens pallens mosquitoes, and will lead to novel diagnosis methods for resistance. Thus, the proposed research will greatly enhance the monitoring and management of insecticide resistance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI075746-05
Application #
8289217
Study Section
Special Emphasis Panel (ZRG1-IDM-R (50))
Program Officer
Costero, Adriana
Project Start
2007-07-01
Project End
2013-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
5
Fiscal Year
2012
Total Cost
$94,638
Indirect Cost
$6,428
Name
Nanjing Medical University
Department
Type
DUNS #
420026593
City
Nanjing
State
Country
China
Zip Code
21002-9
Zou, F F; Guo, Q; Sun, Y et al. (2016) Identification of protease m1 zinc metalloprotease conferring resistance to deltamethrin by characterization of an AFLP marker in Culex pipiens pallens. Parasit Vectors 9:172
Lv, Yuan; Wang, Weijie; Hong, Shanchao et al. (2016) Comparative transcriptome analyses of deltamethrin-susceptible and -resistant Culex pipiens pallens by RNA-seq. Mol Genet Genomics 291:309-21
Liu, Bingqian; Tian, Mengmeng; Guo, Qin et al. (2016) MiR-932 Regulates Pyrethroid Resistance in Culex pipiens pallens (Diptera: Culicidae). J Med Entomol :
Zou, Feifei; Chen, Chen; Zhong, Daibin et al. (2015) Identification of QTLs Conferring Resistance to Deltamethrin in Culex pipiens pallens. PLoS One 10:e0140923
Wang, Weijie; Lv, Yuan; Fang, Fujin et al. (2015) Identification of proteins associated with pyrethroid resistance by iTRAQ-based quantitative proteomic analysis in Culex pipiens pallens. Parasit Vectors 8:95
Lv, Yuan; Lei, Zhentao; Hong, Shanchao et al. (2015) Venom allergen 5 is Associated With Deltamethrin Resistance in Culex pipiens pallens (Diptera: Culicidae). J Med Entomol 52:672-82
Shi, Linna; Hu, Hongxia; Ma, Kai et al. (2015) Development of Resistance to Pyrethroid in Culex pipiens pallens Population under Different Insecticide Selection Pressures. PLoS Negl Trop Dis 9:e0003928
Lei, Zhentao; Lv, Yuan; Wang, Weijie et al. (2015) MiR-278-3p regulates pyrethroid resistance in Culex pipiens pallens. Parasitol Res 114:699-706
Zhou, Dan; Liu, Xianmiao; Sun, Yan et al. (2015) Genomic Analysis of Detoxification Supergene Families in the Mosquito Anopheles sinensis. PLoS One 10:e0143387
Fang, Fujin; Wang, Weijie; Zhang, Donghui et al. (2015) The cuticle proteins: a putative role for deltamethrin resistance in Culex pipiens pallens. Parasitol Res 114:4421-9

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