Transmission and coevolutionary dynamics drive the evolution of generalist and specialist viruses
Lead Research Organisation:
UNIVERSITY OF EXETER
Department Name: Biosciences
Abstract
Viruses show tremendous diversity in the hosts that they attack - both generalists and specialists are common in nature. Unlike specialists, generalist viruses are able to infect a range host species, whereas specialists infect a single host type. What explains this variation in the types of interactions between hosts and their viruses? How do viruses and their hosts interact? Can the way they interact evolve over time? Answers to these questions are central to understanding the dynamics of disease. The underlying processes governing viral-host interactions are highly complex - ranging from molecular and cellular through to population and multi-trophic levels - and crucially depend on the interplay between ecology and coevolution, a process of simultaneous evolution of hosts and viruses in response to each other. However, this complexity presents numerous challenges to achieving a mechanistic understanding of disease dynamics.
The proposed research will investigate the evolution of specialist and generalist viruses - from genes to cells to populations to the community. It will consider how hosts and viruses evolve simultaneously and in response to each other, paying particular attention to how viruses are transmitted. The novel approach proposed here will intertwine experimental evolution and mathematical models, using the bacteria, Escherichia coli and viruses that attack bacteria, bacteriophages, as a model system that can help us understand virus evolution in nature. Experiments will document coevolution in real-time and directly test theoretical predictions put forth by the theoretical framework. At the same time, data generated from the experiments will be incorporated into a new generation of mathematical models that will provide a range of both specific and general predictions regarding the evolution of specialist and generalist viruses. The results of this work will further our general understanding of the dynamics of disease.
The proposed research will investigate the evolution of specialist and generalist viruses - from genes to cells to populations to the community. It will consider how hosts and viruses evolve simultaneously and in response to each other, paying particular attention to how viruses are transmitted. The novel approach proposed here will intertwine experimental evolution and mathematical models, using the bacteria, Escherichia coli and viruses that attack bacteria, bacteriophages, as a model system that can help us understand virus evolution in nature. Experiments will document coevolution in real-time and directly test theoretical predictions put forth by the theoretical framework. At the same time, data generated from the experiments will be incorporated into a new generation of mathematical models that will provide a range of both specific and general predictions regarding the evolution of specialist and generalist viruses. The results of this work will further our general understanding of the dynamics of disease.
Technical Summary
Viruses show tremendous diversity in host-use strategies - both generalists and specialists are common in nature - thus the questions of how, when and why these strategies evolve have long intrigued epidemiologists. Yet, the causal mechanisms underlying the evolution of generalist and specialist viruses remain unclear.
We will use a pioneering combination of experimental evolution (with E.coli-lambdavir and E.coli-T3 systems) and mathematical modeling across multiple biological scales to investigate (a) molecular and environmental basis for variation in viral-host interactions; (b) if these interactions change over the course of coevolution; and (c) the effects of transmission dynamics on evolutionary change. The mathematical and experimental approaches will be developed in parallel, merging recent eco-evolutionary theory and epidemiology to advance our understanding of the dynamics of infectious disease in novel directions. A key component of our approach is the ability to provide a general understanding of the ecology and evolutionary of viral-host dynamics beyond our specific study system (Forde et al. 2008).
Our project combines the following innovative approaches:
1. A mathematical modeling framework designed to bridge the gap between laboratory experiments and the dynamics of naturally occurring diseases.
2. An experimental evolution approach that will allow us to manipulate evolution of viral infection strategies using bioengineering to directly test our theoretical predictions.
Our interdisciplinary approach of combining molecular details of viral-host interactions into an ecological and coevolutionary framework will provide new insights into long-standing questions of the role of transmission dynamics in the evolution of viral infection strategies, and critically inform research in natural viral-host systems.
We will use a pioneering combination of experimental evolution (with E.coli-lambdavir and E.coli-T3 systems) and mathematical modeling across multiple biological scales to investigate (a) molecular and environmental basis for variation in viral-host interactions; (b) if these interactions change over the course of coevolution; and (c) the effects of transmission dynamics on evolutionary change. The mathematical and experimental approaches will be developed in parallel, merging recent eco-evolutionary theory and epidemiology to advance our understanding of the dynamics of infectious disease in novel directions. A key component of our approach is the ability to provide a general understanding of the ecology and evolutionary of viral-host dynamics beyond our specific study system (Forde et al. 2008).
Our project combines the following innovative approaches:
1. A mathematical modeling framework designed to bridge the gap between laboratory experiments and the dynamics of naturally occurring diseases.
2. An experimental evolution approach that will allow us to manipulate evolution of viral infection strategies using bioengineering to directly test our theoretical predictions.
Our interdisciplinary approach of combining molecular details of viral-host interactions into an ecological and coevolutionary framework will provide new insights into long-standing questions of the role of transmission dynamics in the evolution of viral infection strategies, and critically inform research in natural viral-host systems.
Planned Impact
The proposed research will be of exceptionally broad interest. Naturally, it will be of interest to those working epidemiology and the evolution of virulence, where more general infection models are usually assumed. In addition, explicitly addressing the coevolutionary dynamics of infectious disease is becoming a leading approach in biomedical research, with applications ranging from reliable molecular diagnostics to monitoring pathogenicity. Our results will provide the biomedical and epidemiological communities with data based on precisely modelled interactions between hosts and viruses that are experimentally verified. Our results will improve public health initiatives through increasing our understanding of the ecology and evolution underlying pathogen infection strategies.
The proposed research provides a middle ground between the relative simplicity of current mathematical models and the complexity of field studies, and thus will allow us to identify those components of both theory and empirical work that are likely to be generalisable to other host-viral systems. Furthermore, our results will be of interest to those working in ecology and evolution, and host-parasite interactions in general. In addition, the proposed work will provide a better understanding regarding the ecology and evolution of microbes. Microorganisms are ubiquitous, abundant and mediate environmental processes of great importance.
The proposed research provides a middle ground between the relative simplicity of current mathematical models and the complexity of field studies, and thus will allow us to identify those components of both theory and empirical work that are likely to be generalisable to other host-viral systems. Furthermore, our results will be of interest to those working in ecology and evolution, and host-parasite interactions in general. In addition, the proposed work will provide a better understanding regarding the ecology and evolution of microbes. Microorganisms are ubiquitous, abundant and mediate environmental processes of great importance.
People |
ORCID iD |
Ivana Gudelj (Principal Investigator) |
Publications
Sieber M
(2014)
Dispersal network structure and infection mechanism shape diversity in a coevolutionary bacteria-phage system.
in The ISME journal
Sieber M
(2014)
Do-or-die life cycles and diverse post-infection resistance mechanisms limit the evolution of parasite host ranges.
in Ecology letters
Rashkov P
(2016)
Kinase Inhibition Leads to Hormesis in a Dual Phosphorylation-Dephosphorylation Cycle.
in PLoS computational biology
Gudelj I
(2016)
Stability of Cross-Feeding Polymorphisms in Microbial Communities.
in PLoS computational biology
Description | We have developed a new theory that provides an explanation of why most parasites are specialists (have narrow host ranges). This work was published in Ecology Letters (impact factor 13) We have also shown demonstrate that the effects of dispersal on diversity in coevolving host-parasite systems depend on an intricate interplay of the structure of the underlying dispersal network and the specifics of the host-parasite interaction. Published in ISME Journal (impact factor 9). In addition we have shown that environment-specific differences in the cost of host resistance to viruses are not required, as previously throughout, to generate differences in host diversity. Our work underscores the importance of the genetic and functional context of the point of interaction between hosts and viruses in coevolutionary interactions. This work is currently in review in ISME Journal. |
Exploitation Route | Our research has been addressing a critical gap in epidemiological research: explicit linkages between the genetic, ecological and evolutionary mechanisms underlying the evolution of infection strategies. The work has advanced our understanding of the evolution of viral infection strategies - a key step towards developing a comprehensive understanding of the ecology and evolution of infectious disease. We will use this research to communicate the importance of mathematical modelling for infectious diseases to a number of school outreach programs. In addition our work has been published in high impact journals. |
Sectors | Agriculture, Food and Drink,Education,Healthcare |
Description | AstraZeneca funding |
Amount | £40,000 (GBP) |
Organisation | AstraZeneca |
Sector | Private |
Country | United Kingdom |
Start | 10/2014 |
End | 10/2016 |
Description | ERC Proof of Concept |
Amount | € 180,000 (EUR) |
Funding ID | MuFLOART |
Organisation | European Research Council (ERC) |
Sector | Public |
Country | Belgium |
Start | 10/2018 |
End | 03/2020 |
Description | Bacteria-phage coevolution |
Organisation | University of California, Santa Cruz |
Department | Department of Ecology and Evolutionary Biology |
Country | United States |
Sector | Academic/University |
PI Contribution | This collaboration was funded by a BBSRC/NSF EEID grant and involves interdisciplinary work: mathematical modelling conducted in Gudelj lab (Exeter University) and experimental evolution conducted in Forde lab (UC Santa Cruz). |
Collaborator Contribution | This collaboration was funded by a BBSRC/NSF EEID grant and involves interdisciplinary work: mathematical modelling conducted in Gudelj lab (Exeter University) and experimental evolution conducted in Forde lab (UC Santa Cruz). |
Impact | This is a interdisciplinary collaboration involving mathematical modelling (Gudelj) and experimental evolution (Forde). This collaboration has resulted in a number of high impact publications including Nature, Ecology Letters and ISME Journal |
Description | Darwinian Evolution Applied to Cancer |
Organisation | AstraZeneca |
Country | United Kingdom |
Sector | Private |
PI Contribution | Provide expertise in developing mathematical models of Darwinian microbial evolution and applying them to cancer |
Collaborator Contribution | Providing data relating to evolution of resistance in cancers and providing cancer-related expertise |
Impact | Currently writing first of many paper for publication. AstraZeneca will continue financial support and collaboration in the future. |
Start Year | 2014 |
Description | International conference: Coevolution - Models and Microbial Model Systems |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Coevolution is a fundamental process in evolution. The aim of this workshop is to bring together empiricists using experimental evolution to study coevolution with theoreticians to develop new modelling approaches and to highlight exciting new developments of coevolutionary theory requiring experimental tests. |
Year(s) Of Engagement Activity | 2010 |
URL | http://www.mmems.org |
Description | Radio Serbia interview |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Media (as a channel to the public) |
Results and Impact | discussing mathematics for biology in a radio program "A step towards science" |
Year(s) Of Engagement Activity | 2015 |