VIAR · Virus-induced autophagy restriction
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2018-04-01 → 2020-03-31
- Финансиране от ЕС
- 171 461 €
- Участници
- 1
- Схема
- MSCA-IF-EF-RI
Линиите свързват координатора с партньорите.
Накратко на български
Автофагията е механизъм, с който клетките унищожават вирусни компоненти, но HIV е развил стратегии за избягване на тази защита. Разбирането на този процес помага при търсенето на нови начини за стимулиране на клетъчния имунитет срещу вируса.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Virus-induced autophagy restriction
Cellular innate immunity employs multiple ways to fight against invading pathogens, among them autophagy. During autophagy cytoplasmic cargoes, such as viral components, are targeted for destruction. This process has been previously recognized as an anti-viral mechanism against e.g. human immunodeficiency virus (HIV). However, HIV has evolved strategies to counteract this anti-viral defense system. While the basic core machinery of autophagy is well-described, the virus-autophagy interplay is little understood. The overall goal of this project was to (I) define cellular key factors restricting anti-viral autophagy that may be promising targets to therapeutically inhibit and boost autophagy and (II) to examine HIV autophagy evasion strategies. Thus, we intend to ultimately advance our understanding of the intricate interplay between cellular autophagy and the virus, which may be the basis for future innovative anti-viral therapeutic strategies.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Cellular innate immunity employs multiple ways to fight against invading pathogens, among them autophagy. Autophagy is an evolutionarily conserved homeostatic process in which damaged or surplus proteins are engulfed by double-membranes and subsequently degraded by the lysosome. Although initially described as non-specific, it has become evident that autophagy can selectively recognize and degrade cargos. While many pro-autophagy and therefore anti-viral factors have been studied in detail, our knowledge about prevention of excessive and imbalanced autophagy is limited. Autophagy has been previously recognized as a viral restriction mechanism for e.g. HIV. Even though HIV infection triggers autophagy, the virus evolved strategies to diminish this response by exploiting cellular factors, although key players and mechanisms involved are currently not well characterized. Moreover, since inhibition of enzymes by drugs is easier than activation, pro-viral autophagy restriction factors are promising targets for therapeutic approaches aiming to boost the autophagy. This proposal aims to combine expertise of the host (HIV) and the researcher (autophagy) to identify novel cellular pro-viral proteins mediating the restriction of autophagy using HIV as a model system. Human cells containing an autophagic flux reporter construct will be sorted according to autophagic flux after CRISPR/Cas9 mediated knockout of single proteins and gRNAs enriched in cells with high autophagic flux determined and HIV infection. Proteins identified in the innovative screen will be characterized in detail determining molecular mechanisms and viral interaction partners. Thereby, we gain fundamental insight into the balanced regulation of cellular autophagy upon viral challenges as well as viral evasion strategies. Furthermore, identified factors and molecular mechanisms will be relevant to unravel underlying mechanisms of diseases with imbalanced autophagy such as cancer and inflammatory diseases.
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSITAET ULM · UlmКоординаторГермания
Връзки
Данни: CORDIS, © Европейски съюз