PhD defence Eleanor Marshall

Written by OneHealthPact on February 5, 2025. Posted in News.

On Thursday 13 February 2025 Eleanor Marshall, one of our 26 PhD’s, will defend her PhD thesis titled: ‘Storming the Castle – Usutu virus vs. West Nile virus: insights into neuroinvasion’.

Three main insights

1. West Nile virus appears far more able to induce neurological disease in humans compared to Usutu virus, despite their close relation and similarities in transmission cycle, prevalence and geographical distribution. We hypothesized that, when compared to West Nile virus, Usutu virus may be less able to infect the brain, or be less able to gain access to the brain.

2. In her thesis she found that both West Nile virus and Usutu virus could infect and replicate within two very different models of the human brain, and use the same mode of neuroinvasion across an innovative model of the human blood-brain barrier. However, West Nile virus consistently grew to higher titres than Usutu virus. In a model of human spinal cord motor neurons she saw that Usutu virus was not able to infect or replicate due to induction of a robust immune response, whereas West Nile virus did not induce such a response and was therefore well able to infect these cells.

3. These data may explain the differences observed in the severity and incidence of disease resulting from infection with these viruses, as Usutu virus might not be able to use an important route of neuroinvasion along the spinal cord into the brain, and may replicate to lower titres even if it gains access across the blood-brain barrier. However, individuals with a defective immune response may still be at risk of neuroinvasion via the spinal cord during Usutu virus infection. Combined with these findings, we have developed and employed a range of robust, relevant models of neuroinvasion and neurovirulence that could be rapidly applied to assess the risk to human health posed by new and emerging viruses.