Understanding interactions among respiratory viruses
Supervisor: Professor Pablo Murcia, School of Infection and Immunity
The human respiratory tract hosts a community of viruses that cause outbreaks, epidemics, and pandemics. Respiratory viruses have been traditionally studied in isolation and we know very little about the biological and epidemiological consequences of their interactions. However, we have shown that the interplay among respiratory viruses has an impact in their epidemiology (Nickbakhsh et al., 2019). The aims of this project are i) to identify previously unknown interactions among respiratory viruses; ii) to characterise the nature and mechanisms by which viruses interact; and iii) to integrate the impact of virus-virus interactions from the cellular to the population level. We will perform experimental infections of air-liquid interface cellular cultures representing the human respiratory tract and characterise the infection and co-infection phenotype of key respiratory viruses as we have previously shown (Dee et al., 2021). To study virus interactions at the cellular level we will combine classical virology, transcriptomics and image analyses, whereas to study changes in virus structure we will use cryo-electron microscopy (Haney et al., 2021). To estimate the population impact of the observed virus-virus interactions we will perform mathematical modelling (Dee et al., 2021; Nickbakhsh et al., 2019). This programme will provide fundamental new information on the complex biology of multi-pathogen systems and inform the design of control interventions. It will also change future research approaches to study viral infections.
References
Dee, K., Goldfarb, D. M., Haney, J., Amat, J. A. R., Herder, V., Stewart, M., . . . Murcia, P. R. (2021). Human rhinovirus infection blocks SARS-CoV-2 replication within the respiratory epithelium: implications for COVID-19 epidemiology. J Infect Dis. doi:10.1093/infdis/jiab147
Haney, J., Vijayakrishnan, S., Streetley, J., Dee, K., Goldfarb, D., Clarke, M., . . . Murcia, P. R. (2021). Generation of chimeric respiratory viruses with altered tropism by coinfection of influenza A virus and respiratory syncytial virus. bioRxiv.
Nickbakhsh, S., Mair, C., Matthews, L., Reeve, R., Johnson, P. C. D., Thorburn, F., . . . Murcia, P. R. (2019). Virus-virus interactions impact the population dynamics of influenza and the common cold. Proc Natl Acad Sci U S A. doi:10.1073/pnas.1911083116
Haney, J., Vijayakrishnan, S., Streetley, J., Dee, K., Goldfarb, D., Clarke, M., . . . Murcia, P. R. (2022). Generation of chimeric respiratory viruses with altered tropism by coinfection of influenza A virus and respiratory syncytial virus. Nature Microbiology. doi: 10.1038/s41564-022-01242-5.