Viral infections in the brain: how viruses enter, infect, and get transported by neurons

While infection of neurons is the hallmark of bona fide neurotropic viruses such as rabies and some herpesviruses, the possibility that viruses such as SARS-CoV-2 could infect neurons or glial cells in our brain is less well documented, with reports that show contradictory results.

Up to one third of COVID-19 patients suffer from neurological symptoms. Whether these symptoms are due to infection of neurons, glial cells or whether they are an indirect consequence of general inflammation is not clear. SARS-CoV-2 can infect human neurons in cell culture and in the brain of transgenic mice expressing the human receptor of the virus, ACE2, in the respiratory epithelium (K18-hACE2 mice). The mechanisms of cell entry and spreading in neurons have not been elucidated.

The question we want to address is if these neurological symptoms can be caused by low-level infection of neurons or glial cells that remains undetected in non-fatal cases and that may cause neurological complications of different duration.

To address this question, we established collaboration with Prof. Jari Koistinaho, head of the Neuroscience Center in Helsinki, and Prof. Anja Kipar, pathologist at the University of Zurich with extensive experience in SARS-CoV-2 animal models. We grow human neurons or glial cells from induced pluripotent stem cells (iPSC) as monotypic- or co-cultures in 96-well plates that are suitable for high-resolution automated imaging. Novel combinatorial antiviral strategies, specifically formulated to block neuronal infection, are being developed and tested in cell culture and animal models.

This research direction of ours is sponsored by EU Horizon 2021-2027 program.