Neurotropic viruses, including herpesviruses, rabies virus, and poliovirus, initiate infection in the periphery and can move through peripheral neurons to reach the central nervous system (CNS). Since peripheral neurons can be up to one meter long, inefficient neural transport could dramatically affect pathogenesis of neurotropic viruses. This study uses a novel viral “bar-coding” assay to quantify the efficiency of poliovirus transport from the periphery to the CNS in mice. Only 20% of the poliovirus population successfully moved from the periphery to the CNS. Transport of poliovirus in peripheral neurons was very inefficient, and the innate immune response also limited viral movement. Surprisingly, the neural transport barrier was as strong as the innate immune response barrier. Importantly, by overcoming both the neural transport and innate immune barriers, 80% of the poliovirus population successfully moved from the periphery to the CNS, and mice succumbed to disease three times faster than mice with intact barriers. This study identifies inefficient neural transport as a substantial barrier to viral movement in peripheral neurons, which may limit CNS access for many viruses. Peripheral nervous system barriers may contribute to the low incidence of paralytic poliomyelitis in humans, and may also contribute to inefficient trafficking of other neurotropic viruses.
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