H2020Индивидуална стипендия2019–2021

MetAeAvIm · The Role of the Metabolism in Mosquito Immunity against Dengue virus in Aedes aegypti

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-05-01 → 2021-10-30
Финансиране от ЕС: 184 708 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Метаболизмът на комарите Aedes aegypti и конкретните гени, които определят устойчивостта им към вируса на денге, са в центъра на анализа. Разбирането на тези процеси помага за разработването на нови стратегии за контрол на насекомите, които пренасят заболяването.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

The Role of the Metabolism in Mosquito Immunity against Dengue virus in Aedes aegypti

Mosquito-borne diseases remain among the most prevalent diseases in the world. For example, estimates suggest that the Dengue virus (DENV) causes 400 million infections every year. At present, more than half of the world population lives in areas where mosquito vectors are present, and this is predicted to expand as a result of climate change. In that sense, the manipulation of vector competence is a potential tool for the development of new strategies of vector control. However, the incipient understanding of antiviral mechanisms has limited developments in this field. DENV, the causative agent of dengue fever, is a single positive-strand RNA flavivirus primarily transmitted by A. aegypti. Following ingestion by the mosquito in a blood meal, DENV is able to invade midgut epithelial cells. During this process, the mosquito immunity is modulated by its physiological state and nutritional status. By focusing on the analysis of metabolic pathways by gene set enrichment analysis, we identified 17 biological pathways that were enriched in at least 3 out of 4 populations, suggesting that these pathways play a conserved role in the acquisition of resistance against DENV. With this in mind, we proposed to study the metabolism of mosquitoes and to identify metabolic pathways and genes that are determinants for DENV resistance. We additionally proposed to test whether these pathways could be explored in transgenic mosquitoes to modulate vector competence.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Mosquito-borne diseases remain among the most prevalent diseases in the world with. At present, more than half of the world population lives in areas where mosquito vectors are present. Vector control is one of the cornerstones of arbovirus control. However, insecticide-resistant population are emerging demanding new tools of vector control to be developed. It is known that mosquito immunity can be modulated by its physiological state and nutritional status. However, we still lack an integrated view of how immune mechanisms and metabolic pathways interact to control viruses at different stages of infection. In order to obtain a more detailed understanding of the gene expression profile associated with immunity to Dengue virus (DENV), we performed a genome-wide analysis of the transcriptome of susceptible and resistant individuals from the same population of mosquitoes. Metabolic pathways represented the majority of the differentially expressed gene sets identified by our analysis, suggesting that differences in metabolism determine DENV resistance. These results support the hypothesis that mosquito metabolism plays a key role in controlling mosquito susceptibility to viral infections. In this project, we will characterize the metabolism of mosquitoes and characterize pathways and genes that are determinants for DENV resistance. We will study the metabolism of A. aegypti, comparing susceptible and resistant mosquitoes, measuring specific metabolic outputs and also performing unbiased high-throughput metabolomic studies. In parallel, we will perform reverse genetic screenings to validate whether metabolic pathways and biological processes identified in our transcriptomic analysis have a role in vector competence to DENV. Finally, we will apply the CRISPR/Cas9 technology and classical transgenesis to target genes and pathways that affect vector competence in mosquitoes. Together, this project will allow for a deeper mechanistic study of mosquito antiviral immunity.

Оригинален текст от CORDIS (на английски).

Участници

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisКоординаторФранция