Viral tools and monosynaptic tracers for studying SARS-CoV2 neurotropism and neuronal transmission

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There is accumulating evidence that the pandemic SARS-CoV2 can infect cells of the CNS. Infection of olfactory neurons may be responsible for the loss of taste and smell and infection of the brainstem for respiratory failure of critically ill COVID-19 patients. Transneuronal transfer from peripheral nerves to the CNS has been described before for SARS-CoV1. Experimental investigation of the neurotropism and transneuronal spread, by SARS viruses is severely hampered by the requirement for BSL3 laboratories and the low permissivity of mice, which are the major animal models in neurobiology. We have previously established monosynaptic tracing with defective rabies viruses and will here adapt the system to study the neurotropism mediated by the SARS-CoV2 transmembrane Spike protein (S) in human cells, and of S mutants adapted to the mouse receptor mACE2 in mouse cells. In addition to the identification of S target cells, the capacity of S-mediated transsynaptic transmission of viral RNPs will be determined.