A Mutant Vesicular Stomatitis Virus with Reduced Cytotoxicity and Enhanced Anterograde Trans-synaptic Efficiency [post]

2020 unpublished
KEYWORDS neurotropic virus, output network tracing, vesicular stomatitis virus, attenuated 2 cytotoxicity, enhanced anterograde trans-synaptic tracing 3 Abstract Understanding the connecting structure of brain network is the basis to reveal the principle of the brain function and elucidate the mechanism of brain diseases. Trans-synaptic tracing with neurotropic viruses has become one of the most effective technologies to dissect the neural circuits. Although the retrograde trans-synaptic
more » ... ans-synaptic tracing for analyzing the input neural networks with recombinant rabies and pseudorabies virus has been broadly applied in neuroscience, viral tools for analyzing the output neural networks are still lacking. The recombinant vesicular stomatitis virus (VSV) has been used for the mapping of synaptic outputs. However, several drawbacks, including high neurotoxicity and rapid lethality in experimental animals, hinder its application in long-term studies of the structure and function of neural networks. To overcome these limitations, we generated a recombinant VSV with replication-related N gene mutation, VSV-NR7A, and examined its cytotoxicity and efficiency of transsynaptic spreading. We found that VSV-NR7A exhibits attenuated cytotoxicity, delayed but enhanced anterograde trans-synaptic tracing efficiency, compared with the wild-type VSV. Our work could provide an improved tool for structural and functional studies of neurocircuit.
doi:10.21203/rs.2.21708/v1 fatcat:s4ak3ex3yfbnlnzmsdzqwpwvoe