Viral encephalitis (VE) is a serious and debilitating disease, with high rates of mortality and long-term sequelae. The efficacy of medical intervention on VE is often dependant on the stage of infection; once a patient is symptomatic, treatment options are often limited. Despite the clear need to identify infected individuals prior to symptomatic onset, developing a diagnostic tool is problematic, due to ethical and practical limitations of experimental models.
To circumvent these limitations, we have established and characterised a human stem cell derived neuronal model to investigate the host response to infection using multiple neurotropic viruses. This has enabled study of viral pathogenesis in a relevant in vitro model, and forms a foundation for biomarker discovery. Using next-generation sequencing, we have identified microRNAs that are differentially expressed (adjusted P-value <0.05) when stem cell derived neurons are infected with several strains of Rabies virus, including a laboratory adapted strain and several wild type isolates. MicroRNAs (miRNAs) are small non-coding RNAs that show promise as biomarkers of a range of diseases, including cancer and diabetes. Here, viral-induced miRNA changes allow discrimination between mock, lab-adapted, and wild type infected samples, highlighting the diagnostic potential of these transcripts. Along with parallel in vivo studies and additional viral species (Hendra and West Nile viruses), these results will form a biomarker signature of VE. Establishing this model and interrogating the response to infection has required expertise from stem cell biology, virology, and bioinformatics.
This cross-disciplinary project is the first step in developing next-generation diagnostics for the prompt detection of VE. The potential translation of this research into a diagnostic platform continues to be examined with the input of engineering and nanofabrication experts. A diagnostic platform for VE would allow early, effective intervention that would save lives.