HAAIV · Adaptive evolutionary pathways of highly pathogenic avian H5N1 influenza in humans
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2015-11-01 → 2017-10-31
- EU contribution
- €177,599
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Adaptive evolutionary pathways of highly pathogenic avian H5N1 influenza in humans
- What is the problem/issue being addressed? Highly pathogenic H5N1 influenza viruses are endemic in wild birds and poultry across several Asian countries, and continue to cause human infections with high mortality. Global concern persists that these avian influenza viruses will evolve into viruses that can efficiently transmit between humans and may then cause a severe influenza pandemic. However, estimating the real risk of such a pandemic scenario is difficult due to limited understanding of the evolutionary requirements of H5N1 viruses to cross the species barrier and adapt to humans. There is therefore an urgent need to increase our insight into H5N1 influenza evolution within the human host and identify and characterize previously unrecognized adaptive evolutionary pathways. - Why is it important for society? In view of the continuing widespread circulation amongst birds and occurrences of severe human infections, global concerns persist of an imminent devastating H5N1 pandemic if these viruses were to evolve towards efficient transmission between humans. This concern is reinforced by recent experimental research in ferrets showing that airborne transmission of H5N1 viruses only would require a limited number of genetic changes. The focus of the proposed project is to better understand the pandemic risk of HPAI H5N1 viruses by detailed analyses of viral evolution during actual human infections in Indonesia and Vietnam and phenotypic characterization of viral variants observed during these infections. Society and in particular policy makers and public health authorities can benefit from this research by using the results of the research to improve our ability to predict, prevent and intervene in outbreaks of HPAI H5N1. - What are the overall objectives? The aim of the proposed research is to identify evolutionary pathways involved in adaptation of avian influenza viruses to humans. This aim will be achieved by using whole genome virus sequence analyses from clinical specimens obtained from birds and H5N1-infected patients (Aim 1), followed by phenotypic characterization of mutations potentially relevant for human adaptation using recombinant viral proteins and viruses (Aim 2)
Data: CORDIS, © European Union
Project objective
Highly pathogenic H5N1 influenza viruses are endemic in wild birds and poultry across several Asian countries, and continue to cause human infections with high mortality. Global concern persists that these avian influenza viruses will evolve into viruses that can efficiently transmit between humans and may then cause a severe influenza pandemic. However, estimating the real risk of such a pandemic scenario is difficult due to limited understanding of the evolutionary requirements of H5N1 viruses to cross the species barrier and adapt to humans. There is therefore an urgent need to increase our insight into H5N1 influenza evolution within the human host and identify and characterize previously unrecognized adaptive evolutionary pathways. To gain this understanding we propose to apply whole genome, next generation viral quasispecies sequencing directly from serial clinical specimens obtained from H5N1-infected patients. We will perform an in-depth characterization of mutations that are selected during human H5N1 infections and include all influenza virus genes in our analyses. These analyses will provide insight into the diversity of H5N1 quasispecies and the molecular mechanisms of human adaptive mutations. This unbiased whole genome sequencing approach of the dynamics of within-host evolution of quasispecies during the course of infection in serial clinical specimens is highly innovative. The detection of minority variants that expand during the course of infection represents a unique approach to identify adaptive viral evolutionary pathways.
Original text from CORDIS.
Participants
- ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM · AmsterdamCoordinatorNetherlands
Links
Data: CORDIS, © European Union