MMXVI · Minimal Model for Pox-Virus Infection
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2017-06-01 → 2019-05-31
- EU contribution
- €183,455
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Minimal Model for Pox-Virus Infection
The initial contact between a virus particle and its host is a crucial step during infection. The process depends on nanoscale structural changes that due to technical limitations remain a major challenge in infection biology. Methods such as fluorescence or electron microscopy provide either the required molecular specificity or resolution to investigate such changes. Recent developments in super-resolution microscopy allow the visualization of cellular and viral structures at resolutions in the range of tens of nanometers and therefore provide new tools to address the dynamics of virus architectural changes during the first stages of infection. The focus of the project was investigating protein structure-function relationships within the prototypic poxvirus, vaccinia. However, the model system and imaging tools are broadly applicable to other biological systems such as different viruses. A better understanding of virus host interactions benefits society in general as it may serve as a foundation to new antiviral strategies. The overall objectives were to develop and implement a novel minimal model of virus infection based on cell-derived membrane blebs to investigate virus host interactions using vaccinia. The project addressed the nanoscale virus architecture, particularly at the membrane level, by combining single-molecule techniques with membrane blebs. Furthermore, the dynamics of protein organization in the viral membrane were investigated. Based on our findings, we propose that polarization and clustering of the entry fusion compley of vaccinia virus is critical for efficient virus-cell fusion and entry of the viral particle. The nanoscale organization of the poxvirus membrane suggests that virion protein architecture is critical to virus function. In conclusion, the organization of the vaccinia virus membrane into functionally distinct domains may have evolved as a mechanism to maximise virion binding and fusion efficiency for productive infection.
Data: CORDIS, © European Union
Project objective
Viral diseases represent one of the world’s highest socio-economic burdens. Increased global trade and travel, climate change resulting in shifting viral vectors, and the emergence of new and often deadly viruses is inevitable. Therefore, detailed understanding of the complexity of virus particles and the development of new model systems to study them, will be essential to develop new research, diagnostic, and therapeutic tools. The structural changes that occur during the initial contact between a virus and its host remains one of the major challenges in infection biology. Until recently, the investigation of viral nano-architecture and dynamic changes that occur in virus particles during the infectious lifecycle was limited to methods, such as EM, with no capacity to capture dynamic events or define molecular specificity. The goal of the proposed project is to create a new minimal model of virus infection based on cell-derived membrane blebs. The model will be amenable to novel super-resolution microscopy (SRM) methods that allow the visualization of viral structures at resolutions of tens of nanometers. Recently developed analytical tools like single-virion averaging allows the generation of precise models from hundreds of events. This affords unprecedented insights into the biological and biophysical requirements of virus infection. Furthermore, we aim to investigate the dynamics of virus architectural changes during the first stages of infection, particularly at the membrane level, by combining single-molecule techniques with our new model-system. While initially aimed at investigating protein structure-function relationships within the prototypic poxvirus, vaccinia, the model system and imaging developments outlined will be broadly applicable to a wide range of biological systems including other viruses. Thereby, this proposal looks to advance the field of infection biology into the nanoscale.
Original text from CORDIS.
Participants
- UNIVERSITY COLLEGE LONDON · LondonCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union