Virus mixing in the porcine respiratory tract – a pandemic mixing vessel?

Pigs have long been viewed as a “mixing vessel” where novel pandemic influenza viruses can be generated by reassortment of avian and mammalian-adapted influenza A viruses (IAVs) – most recently exemplified by the 2009 H1N1 influenza pandemic [1]. Reassortment of IAV strains requires simultaneous infection of a single cell with two strains of IAV, but paradoxically, avian and human strains of the virus preferentially infect different cell populations in the respiratory tract because of differing receptor specificities. Recently, in vitro co-infection of human airway cells with IAV and the unrelated virus respiratory syncytial virus (RSV) has been shown to lead to the formation of hybrid virus particles that use the RSV envelope protein to deliver the IAV genome to cells that IAV would normally not infect [2]. We will use recently developed tissue and organ culture models of the porcine respiratory tract to test if co-infection with porcine respiratory coronavirus (PRCV) and IAV also leads to hybrid viruses and if so, whether this can extend the cell tropism and facilitate reassortment of IAV strains. In parallel, we will also investigate the effects that IAV receptor specificity and filamentous or spherical budding morphology [3] has on viral reassortment. The project will use cutting edge techniques of array tomography combined with correlative fluorescence imaging and serial section block face electron microscopy to characterise virus budding morphology at the sub cellular level, and viral genetics to study the affects of co-infection on IAV reassortment.

This studentship will provide excellent training in virological and imaging skills as well as broad experience in the fields of cell biology, biochemistry and molecular biology. The successful candidate will learn and apply a wide variety of techniques and transferable skills.