H2020Индивидуална стипендия2017–2019

EvolVir · Evolution of virulence in immune-compromised hosts and the adaptation of emerging viruses

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

Период: 2017-07-01 → 2019-06-30
Финансиране от ЕС: 195 455 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Влиянието на слабия имунитет върху еволюцията на вирусите се проучва чрез опити с плодови мухи. Това помага да се разбере как различната устойчивост на организма променя агресивността на патогените и начина, по който те се разпространяват.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Evolution of virulence in immune-compromised hosts and the adaptation of emerging viruses

Variation in resistance to infection is widespread in natural populations, and it is common to find not only extremely resistant individuals, but also individuals who are extremely susceptible to infection. Individuals that are inherently more susceptible to disease may arise due to specific genetic background, or due to other physiological aspects such as sex, age, nutrition levels or prior infection history. In host-pathogen systems, theory predicts that host resistance mechanisms impose strong selection on pathogens, which in turn evolve counter-defences to avoid those mechanisms. While pathogen mediated selection is thought to drive genetic variation in host resistance levels, host immunity is also a strong evolutionary force shaping patterns of pathogen virulence. Some theory predicts that highest host resistance will favour the evolution of increased pathogen virulence. The aim of this project was to test the role of immune-compromised hosts on the evolution of pathogen virulence, and to dissect the mechanisms that underpin pathogen evolution and transmission in hosts with variable immune responses. Using model fruit flies, I explored the effect of variable host resistance mechanisms on 1) the evolutionary trajectories of pathogens and 2) their spreading capacities. Drosophila offers unique tools and methods to address the effect of host immune-competence as both immune response and gene expression can be easily manipulated and measured. Rearing Drosophila in the laboratory is easy and cost efficient, making fruit flies the ideal host model to measure the impact of single gene mutants on the evolution of pathogens. With this project, we measured in a first set of experiments to what extent host immune-competence may influence the evolution of virulence (phenotype) when passaged on hosts with different immune competences (here males vs. females), to test whether immune-compromised hosts and extreme sex ratio drive pathogen adaptation and if adaptation results in the evolution of more virulent pathogens. In a second set of experiment, we tracked the shedding of pathogen agents from hosts with impaired immune and repair system in epithelial gut cells, as a proxy for disease resistance and transmission of food-borne pathogens.

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

Цел на проекта

Understanding pathogen evolution is key to predicting and managing disease emergence. While theory predicts that strong immune responses will generally select for increased pathogen virulence, current work mostly ignores the effect of immune-suppressed hosts on virulence evolution and on pathogen adaptation to novel hosts during disease spread. Further, the underlying genetic basis of the evolutionary change, that is, the genomic targets of selection, is seldom detected. I will apply a novel experimental approach by evolving the viral pathogen Drosophila C Virus (DCV) in its natural host Drosophila melanogaster, using host lines that are either immune-competent or immune-compromised due to the inactivation of specific immune genes. In addition to assessing changes in the evolution of virulence in these host lines (i.e. viral growth rate and host mortality), I will also take an evolve-and-resequence approach, using ultra-deep sequencing of the viral populations during experimental evolution. Using these uniquely detailed sequence data I will (i) identify the region of the viral genome under selection, (ii) determine if rapid virus adaptation is dependent on the fixation of new mutations or changes in viral variant frequencies from standing genetic variation and (iii) measure the rate of repeatability of pathogen adaptation in identical selective regimes. This work will test the role of immune-compromised hosts on the evolution of pathogen virulence, and also dissect the mechanisms that underpin pathogen evolution during adaptation to hosts with variable immune responses.

Оригинален текст от CORDIS (на английски).

Участници

THE UNIVERSITY OF EDINBURGH · EdinburghКоординаторОбединеното кралство