WEHI PhD Completion Seminar hosted by Dr Marcel Doerflinger

William Clow

PhD Student – Doerflinger Laboratory, Infection and Global Health division, WEHI

Modelling & Targeting Cytokine Storm in Dengue-infected Mice

 

Davis Auditorium

Join via SLIDO enter code #WEHIphdcompletion

Including Q&A session

Followed by refreshments in Tapestry Lounge

Dengue is the world’s most common vector-borne viral infection, with about two thirds of the global population living in Dengue-endemic regions. Symptoms of infection can range from asymptomatic infection through moderate fever to a life-threatening haemorrhagic shock syndrome referred to as severe Dengue. The threat of severe Dengue leads public health experts to recommend that all suspected Dengue cases visit the hospital. This places a heavy burden on health services during outbreaks, as observed in Brazil in 2024, where military field hospitals had to be opened to service the sick. Despite this significant public health risk, there are currently no therapeutics approved for the treatment of Dengue. Effective therapeutics are urgently required to improve disease outcome and expedite patients’ recovery. During my PhD, I explored the use of host-directed therapeutics to address this issue.

Severe Dengue is associated with the onset of cytokine storm, a state of overabundant and dysregulated systemic immune signalling, concurrent with clearance of viral particles from the body. This paradigm suggests that host-directed anti-inflammatory drugs may be effective at preventing or improving the outcome of severe Dengue. Anti-inflammatory drugs have shown clinical efficacy against COVID-19-mediated cytokine storm, which shares many similarities with Dengue that suggest a similar pathogenesis. During my PhD project, I prepared an IFN-deficient severe Dengue mouse model to perform an in vivo screen of multiple clinical-stage therapeutics with known clinical efficacy against COVID-19-mediated cytokine storm. In parallel, I explored new methods to improve the physiological relevance of Dengue mouse models, culminating in a pipeline to drive mouse adaptation of Dengue virus. This work revealed that inhibition of TNF signalling improves disease outcome of infected mice and provided significant insight into the dynamics of Dengue-associated cytokine storm.

All welcome!