H2020Индивидуална стипендия2016–2018

RESTRIVIR · Characterization of a novel mechanism restricting virus infection in reproductive tissues

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

Период: 2016-04-01 → 2018-03-31
Финансиране от ЕС: 185 076 €
Участници: 1
Схема: MSCA-IF-EF-ST

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Накратко на български

Генен механизъм при плодовите мушици ограничава вирусните инфекции в тъканите на репродуктивната система. Това помага да се разбере как се блокира предаването на вируси към следващите поколения.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Characterization of a novel mechanism restricting virus infection in reproductive tissues

Viral infections lead every year to significant losses of human lives, livestock and plant crops, and are responsible for life-threatening pandemics and emerging epidemics, such as infuenza, HIV, ebola or MERS (Middle East Respiratory Syndrome). Viruses are obligatory intracellular pathogens, with a simple RNA- or DNA-based genome, sheltered in a small protein capsid, and hijack the cellular machinery for all stages of their life-cycle. As in other insects and invertebrates, in the model organism Drosophila melanogaster, the main antiviral defence is the small interference (si)RNA pathway. In addition to RNAi, other pathways also participate in restricting viral infections in invertebrates, but their role and relative importance in complementing the RNAi response is not completely characterized Previously, the host laboratory identified a putative novel antiviral restriction mechanism in the follicular somatic cells (FC) of the Drosophila ovarioles. The FC’s constitute an epithelial layer that encapsulates the germline and gives rise to the egg shell. Importantly, these are the last layer of somatic tissue blocking transmission of pathogens to the germline, preventing vertical transmission of viruses. The existence of an additional antiviral pathway in this tissue would then provide an extra layer of protection against virus infection for the next generations. With this project, we set out to identify the genes involved in this new pathway, using a combination of unbiased and targeted genetic screens, genomics and cell culture based assays. The combination of these approached allowed us to discard the involvement of additional RNAi pathways in this novel antiviral mechanism, and led to the identification of seven candidate loci, which are undergoing functional testing.

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

Цел на проекта

Like mammals, insects are infected by many viruses. Among them, arthropod-borne viruses are an increasing worldwide health concern. Insects have potent innate antiviral defenses, of which RNA interference (RNAi) is the main and best studied. In the fruitfly Drosophila melanogaster, the siRNA pathway controls viral replication in somatic tissues. The piRNA pathway, another RNAi based response, acts specifically in the reproductive tract (germline and follicular cells (FC), a monolayer of somatic cells surrounding the germline), to protect the genome against transposon mobilization. Other innate immunity or stress pathways also contribute to the antiviral defense.The host laboratory obtained evidence for a new mechanism controlling viral replication in the FCs of Drosophila. Indeed, a viral replicon derived from Flock House Virus and expressing GFP (FHVΔB2-GFP) is completely derepressed in somatic tissues of mutants for the siRNA pathway, except in FCs, where derepression is partial. No piRNAs of viral origin can be detected in these cells. This viral replicon provides a unique system to decipher a novel pathway restricting viral replication.For this, I will use a combination of forward and reverse genetic screens. EMS mutagenesis, screening for GFP expression and genome resequencing will be used to uncover genes responsible for restricting the replicon in FCs. Next, I will use GFP expression to sort restrictive and permissive FCs in a siRNA pathway mutant followed by RNA sequencing to identify differentially expressed genes. The function of the identified genes will be tested in vivo, using shRNA Drosophila lines. Finally, OSS cells, an FC-derived cell line, will be transformed with the FHVΔB2-GFP replicon to evaluate candidate gene function ex vivo.The identification and characterization of genes involved in a novel viral restriction pathway will increase the knowledge about innate antiviral immunity, an important scientific topic with human health implications.

Оригинален текст от CORDIS (на английски).

Участници

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisКоординаторФранция