Projects per year
Abstract / Description of output
Results: Our in-vitro experiment showed that PAM susceptibility to PRRSV changed considerably over incubation time. Moreover, an increasing proportion of PAMs apparently lacking CD163 were found susceptible to PRRSV at the later incubation stages, thus conflicting with current understanding that CD163 is essential for productive infection of PAMs with PRRSV. We developed process based dynamic mathematical models and fitted these to the data to assess alternative hypotheses regarding potential underlying mechanisms for the observed susceptibility and biomarker trends. The models informed by our data support the hypothesis that although CD163 may have enhanced cell susceptibility, it was not essential for productive infection in our study. Instead the models promote the existence of a reversiblecellular state, such as macrophage polarization, mediated in a density dependent manner by autocrine factors, to be responsible for the observed kinetics in cell susceptibility.
Conclusion: Our dynamic model - inference approach provides strong support that PAM susceptibility to the PRRS virus is transient, reversible and can be mediated by compounds produced by the target cells themselves, and that these can render PAMs lacking the CD163 receptor susceptible to PRRSV. The results have implications for the development of therapeutics aiming to boost target cell resistance and prompt future investigation of dynamic changes in macrophage susceptibility to PRRSV and other viruses.
Keywords / Materials (for Non-textual outputs)
- alveolar macrophages
- host cell susceptibility
- mathematical model
- infection dynamics
- statistical inference
- host-pathogen interaction
FingerprintDive into the research topics of 'Combining Laboratory and Mathematical Models to Infer Mechanisms Underlying Kinetic Changes in Macrophage Susceptibility to an RNA Virus'. Together they form a unique fingerprint.
- 3 Finished
Tenesa, A., Archibald, A., Beard, P., Bishop, S., Bronsvoort, M., Burt, D., Freeman, T., Haley, C., Hocking, P., Houston, R., Hume, D., Joshi, A., Law, A., Michoel, T., Summers, K., Vernimmen, D., Watson, M., Wiener, P., Wilson, A., Woolliams, J., Ait-Ali, T., Barnett, M., Carlisle, A., Finlayson, H., Haga, I., Karavolos, M., Matika, O., Paterson, T., Paton, B., Pong-Wong, R., Robert, C. & Robertson, G.
1/04/12 → 31/03/17
Dutia, B., Archibald, A., Beard, P., Bishop, S., Bronsvoort, M., Burt, D., Collie, D., Digard, P., Freeman, T., Glass, E., Grey, F., Hocking, P., Houston, R., Hume, D., Kaiser, P., Nash, A., Sang, H., Sharp, C., Watson, M. & Whitelaw, B.
1/04/12 → 31/03/17
Porrscon: new tools and approaches to control porcine reproductive and respiratory syndrome(prrs) in the eu and asia
Ait-Ali, T. & Archibald, A.
1/01/10 → 30/06/14