Kinesin-mediated transport of Marek's disease virus

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Marek's disease is a fatal, highly contagious, neoplastic disease affecting chickens. It is caused by an alphaherpesvirus called Gallid herpesvirus-2 or Marek's Disease Virus (MDV). Pathogenesis of the virus can be characterised by exploring virus-host interactions which will enable future interventions that could impede MDV transmission. Therefore, the project aims to uncover the intracellular transport and trafficking of MDV. The virus travels to the nucleus and replicates where it will form viral capsids that will egress via the ER and Golgi for envelopment, then will return to the plasma membrane to infect other neighbouring cells. The virus itself is too large to passively diffuse through the cytoplasm (with a diameter of 200-300 nm), and instead exploits the host's cytoskeleton and motor proteins for cellular transport. It has been implicated that dynein and motors of the kinesin -3 family are instrumental in MDV transport. Therefore, the project will aim to identify how MDV interacts with motor proteins by establishing viral proteins that interact with these motor proteins using proximity-dependent biotinylation and mass spectrometry. As well as this, the binding of the viral candidate proteins with kinesin tails will be investigated to map interaction surfaces on kinesin and viral proteins. Motor protein truncations that lack viral binding sites will be explored and motor mutations in chickens that could potentially limit MDV spread and enhance meat production.