The evolutionary and mechanistic basis of virus host shifts: A Staphylococcaceae-phage system to investigate patterns of virus infectivity and evoluti
Lead Research Organisation:
UNIVERSITY OF EXETER
Department Name: Biosciences
Abstract
The evolutionary and mechanistic basis of virus host shifts: A Staphylococcaceae-phage system to investigate patterns of virus infectivity and evolution across host species
Virus host shifts - where a virus jumps from one host species to another - are a major source of emerging infectious diseases. For example, Ebola, HIV and SARS coronavirus have all jumped into humans from other
species. Despite the importance of emerging viral diseases, we have a limited understanding about what determines the ability of a virus to infect some groups of hosts but not others, or how viruses will evolve in different hosts (Longdon et al. 2014, https://doi.org/10.1371/journal.ppat.1004395). Understanding these processes is vital to predict when and where diseases will emerge in the future.
BACKGROUND
Viruses are disproportionally responsible for emerging infectious diseases, with RNA viruses that normally infect multiple host species considered the most likely to emerge. Additionally, host shifts appear to occur most
often between closely related host species. However, evidence for these hypotheses largely come from comparative data (i.e. observations with no experimental manipulation). Therefore, they point us toward interesting areas for investigation, but cannot tease apart the complex processes explaining the observed patterns.
Experimental studies have highlighted some of the important host-virus interactions that result in successful host shifts (e.g. parvoviruses from cats to dogs (Parrish et al. 2008 http://doi.org/ MMBR.00004-08) but the majority of these studies have been limited to two host systems. Therefore, experimental studies using a wide breadth of host species that vary in their relatedness are essential to make broadly applicable conclusions. Our previous work has used up to 50 species of Drosophila, and their naturally occurring RNA 4 / 15 viruses (Longdon et al. 2011 and 2015 https://doi.org/10.1371/journal.ppat.1002260 and https://doi.org/10.1371/journal.ppat.1004728) to
examine host shifts (video here www.goo.gl/sXBiv5). By using a large number of different host species we are able to find general patterns that apply across host species with varying relatedness.
This project will ask fundamental questions about disease emergence using a bacteriavirus system to study the consequences of virus evolution on host shifts. We will use a panel of over 50 different Staphylococcus
species and a broad host range bacteriophage. This model offers a unique opportunity to perform experiments that would not be possible in a vertebrate-system, and critically will allow us to use experimental evolution to ask fundamental questions about pathogen host shifts. This interdisciplinary project integrates expertise on pathogen host shifts (Ben Longdon, Exeter) and bacteria-phage coevolution (Angus Buckling, Exeter).
Virus host shifts - where a virus jumps from one host species to another - are a major source of emerging infectious diseases. For example, Ebola, HIV and SARS coronavirus have all jumped into humans from other
species. Despite the importance of emerging viral diseases, we have a limited understanding about what determines the ability of a virus to infect some groups of hosts but not others, or how viruses will evolve in different hosts (Longdon et al. 2014, https://doi.org/10.1371/journal.ppat.1004395). Understanding these processes is vital to predict when and where diseases will emerge in the future.
BACKGROUND
Viruses are disproportionally responsible for emerging infectious diseases, with RNA viruses that normally infect multiple host species considered the most likely to emerge. Additionally, host shifts appear to occur most
often between closely related host species. However, evidence for these hypotheses largely come from comparative data (i.e. observations with no experimental manipulation). Therefore, they point us toward interesting areas for investigation, but cannot tease apart the complex processes explaining the observed patterns.
Experimental studies have highlighted some of the important host-virus interactions that result in successful host shifts (e.g. parvoviruses from cats to dogs (Parrish et al. 2008 http://doi.org/ MMBR.00004-08) but the majority of these studies have been limited to two host systems. Therefore, experimental studies using a wide breadth of host species that vary in their relatedness are essential to make broadly applicable conclusions. Our previous work has used up to 50 species of Drosophila, and their naturally occurring RNA 4 / 15 viruses (Longdon et al. 2011 and 2015 https://doi.org/10.1371/journal.ppat.1002260 and https://doi.org/10.1371/journal.ppat.1004728) to
examine host shifts (video here www.goo.gl/sXBiv5). By using a large number of different host species we are able to find general patterns that apply across host species with varying relatedness.
This project will ask fundamental questions about disease emergence using a bacteriavirus system to study the consequences of virus evolution on host shifts. We will use a panel of over 50 different Staphylococcus
species and a broad host range bacteriophage. This model offers a unique opportunity to perform experiments that would not be possible in a vertebrate-system, and critically will allow us to use experimental evolution to ask fundamental questions about pathogen host shifts. This interdisciplinary project integrates expertise on pathogen host shifts (Ben Longdon, Exeter) and bacteria-phage coevolution (Angus Buckling, Exeter).
Organisations
People |
ORCID iD |
| Ben Longdon (Primary Supervisor) | |
| Sarah Walsh (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M009122/1 | 01/10/2015 | 31/03/2024 | |||
| 2237316 | Studentship | BB/M009122/1 | 01/10/2019 | 31/12/2023 | Sarah Walsh |
| BB/T008741/1 | 01/10/2020 | 30/09/2028 | |||
| 2237316 | Studentship | BB/T008741/1 | 01/10/2019 | 31/12/2023 | Sarah Walsh |
| Description | This work has allowed us to show that the genetic relationship between host species (how similar they are) is responsible for a large proportion of the difference in their susceptibility to infection (how well a virus is able to grow in them). We have shown this in a system where we have 64 Staphylococcus hosts, and the pathogen is a bacteriophage called ISP. |
| Exploitation Route | This work has so far developed a model system to investigate virus-host interactions in a multi-host system, allowing us to investigate some of the underlying factors that influence virus-host interactions such as host relatedness. This model system can be used to investigate many aspects of virus-host interactions in the future, such as the influence of local adaptation of a pathogen to a host on its ability to infect subsequent hosts, the role of generalism or specialism on susceptibility, and the underlying molecular mechanisms that contribute to these patterns of susceptibility. |
| Sectors | Other |