Transcriptomics approaches reveal neuronal antiviral immune mechanisms.

Abstract Arthropod-borne viruses exist worldwide and contribute to many neurological infections. Viral infections in the central nervous system (CNS) can lead to virus- and immune-mediated damage of the brain, which can cause severe physical and cognitive defects, or even death. While antiviral responses (such as Type I interferon) have been characterized in the periphery, it is not well understood how innate immune response are coordinated by the various cell types present in the brain. Certain neurotropic arboviruses, such as La Crosse Virus (LACV), predominantly infect neurons; however, it remains unclear how neurons mediate early innate immune responses in the CNS. Upon infection of primary murine cortical neurons and human IPSC-derived cerebral organoids with LACV, we observed widespread infection. Transcriptomics approaches revealed infection of neurons results in the upregulation of interferon-stimulated genes (ISGs) that are also detectable at the protein level. Notably, we found that bystander uninfected neurons have higher ISG expression than neighboring infected cells. Future directions aim to characterize how infected neurons communicate with uninfected bystander neurons during infection. To address this, I have optimized a ProbeSeq pipeline where I infect primary cortical neurons and further characterize infected and uninfected populations using fluorescence in situ hybridization and downstream RNA-sequencing. Supported by the Penn Presidential PhD Fellowship.