SHP-1 Regulates Neuroinvasion of Neurotropic Virus into the CNS (VIR5P.1035)

Abstract Viral infections in the central nervous system (CNS) may have devastating clinical consequences to the host. Neurotropic virus infections often begin in peripheral tissues, which then spread to the CNS via peripheral nerves following entry into nerve terminals by receptor-mediated endocytosis and subsequent retrograde axonal transport into the CNS compartment. In our lab, a possible novel role for the protein tyrosine phosphatase, SHP-1, in regulating neuroinvasion via peripheral nerves of a neurotropic virus (Theiler’s Murine Encephalomyelitis Virus, TMEV) is being investigated. Preliminary data using immunohistochemistry of TMEV showed extensive staining of spinal cord neurons after intraperitoneal inoculation in mice with a null mutation in the SHP-1 gene (me/me mice) compared to wild type mice. Further, intramuscular (IM) inoculations of TMEV caused virus infection in spinal cord neurons and subsequent paralysis of SHP-1-deficient mice but not of wild type mice. IM and intraperitoneal injections (IP) of retrograde axonal transport tracers fluorogold and horseradish peroxidase showed increased tracer levels in the spinal cords of SHP-1-deficient mice compared to wild type mice. Therefore, we propose SHP-1 may play a role in regulating viral neuroinvasion by controlling retrograde axonal transport from peripheral sites of infection. In this sense, SHP-1 may play novel roles in antiviral responses including inhibition of virus invasion and spreading in the CNS.