Studentship: Investigation of the interaction of porcine reproductive and respiratory syndrome viruses with dend. cells implications for pathogenesis and immunity
Lead Research Organisation:
THE PIRBRIGHT INSTITUTE
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
Porcine reproductive and respiratory syndrome (PRRS) is arguably the most important disease of pigs with a huge economic impact globally. The PRRS virus (PRRSV) is rapidly evolving and this is dramatically illustrated by the emergence of highly pathogenic variants in South East Asia [1] and Eastern Europe [2]. There is an urgent need for the development of safer and more efficacious vaccines to improve PRRS control. An improved understanding of the interactions of PRRSV with the immune system would aid the development of the next generation of PRRSV vaccines or novel intervention strategies. To address this need, this project focuses on characterising the interaction of PRRSV with dendritic cells (DCs), a family of specialised cells that play a central role in linking the innate and the adaptive immune systems.
The project will test the hypothesis that increased PRRSV virulence is associated with an enhanced capacity to infect and dysregulate the function of porcine DCs. This will be addressed through the following specific objectives:
1. Compare the susceptibility of defined porcine DC populations to in vitro infection with PRRSV strains spanning a spectrum of pathogenicity.
2. To assess the effects PRRSV strains of differing virulence on the phenotype and function of DC in vitro.
3. To conduct RNA-seq analysis of infected DC to assess global differential gene expression and modulation of host cell response pathways by PRRSV.
4. To use an ex vivo organ explant culture to assess whether enhanced DC infection and modulation of responses also occurs in a key target organ, the tonsil
The project will test the hypothesis that increased PRRSV virulence is associated with an enhanced capacity to infect and dysregulate the function of porcine DCs. This will be addressed through the following specific objectives:
1. Compare the susceptibility of defined porcine DC populations to in vitro infection with PRRSV strains spanning a spectrum of pathogenicity.
2. To assess the effects PRRSV strains of differing virulence on the phenotype and function of DC in vitro.
3. To conduct RNA-seq analysis of infected DC to assess global differential gene expression and modulation of host cell response pathways by PRRSV.
4. To use an ex vivo organ explant culture to assess whether enhanced DC infection and modulation of responses also occurs in a key target organ, the tonsil
Planned Impact
unavailable
| Description | Using in vitro models of porcine macrophages and dendritic cells, we have demonstrated that the pathogenicity of PRRSV-1 strain, SU1-Bel, is not associated with enhanced viral replication but rather with enhanced induction of proinflammatory responses. |
| Exploitation Route | Understanding the molecular mechanisms that lead to enhanced proinflammatory cytokine production may allow the rational design of safe modified live PRRSV vaccines. |
| Sectors | Agriculture Food and Drink |
| Description | Provision of PRRSV field strains |
| Organisation | Animal and Plant Health Agency |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | Experimental heterologous PRRSV challenge model to assess the induction of broadly neutralizing antibodies. Model to assess dendritic cell tropism of PRRS viruses |
| Collaborator Contribution | Provision of PRRSV-1 and -2 field strains |
| Impact | Not yet |
| Start Year | 2016 |
| Description | Provision of PRRSV field strains |
| Organisation | Kansas State University |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Experimental heterologous PRRSV challenge model to assess the induction of broadly neutralizing antibodies. Model to assess dendritic cell tropism of PRRS viruses |
| Collaborator Contribution | Provision of PRRSV-1 and -2 field strains |
| Impact | Not yet |
| Start Year | 2016 |
| Description | Reporter PRRS viruses |
| Organisation | Kansas State University |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | A new application for recombinant reporter PRRS viruses i.e. to use them as a high throughput screen for neutralizing (monoclonal) antibodies. Use as tools to assess the tropism of PRRSV for dendritic cell subsets and the functional consequences. |
| Collaborator Contribution | Provision of plasmids encoding GFP-expressing PRRSV-1 and -2. |
| Impact | Not yet |
| Start Year | 2016 |
| Description | Poster presentation: European Veterinary Immunology Workshop, Utrecht, The Netherlands |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Luke Johnson (PhD student) gave a poster presentation on his studies on the interaction of macrophages and dendritic cells with PRRSV of differing virulence. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Poster presentation: International Pig Veterinary Symposium and International PRRS Symposium, Chongqing, PR China |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Luke Johnson (PhD student) gave a poster presentation on his studies on the interaction of macrophages and dendritic cells with PRRSV of differing virulence. |
| Year(s) Of Engagement Activity | 2018 |