Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Cell & Molecular Biology

First Advisor

Glenn F. Rall

Second Advisor

Susan R. Weiss


Many RNA viruses, following entry into the central nervous system (CNS), remain detectable within the brain long after acute infection has resolved, typically in the absence of clinical signs of CNS disease. In many of these infections, (including measles virus (MV), West Nile virus, sindbis virus, rabies virus, and influenza virus), detection of viral protein or RNAs within the CNS long after the acute phase did not correlate with recovery of infectious virus in infected animals. This led many to consider these residual RNAs as inert viral remnants in neurons that had survived both viral infection and the antiviral host response. In this dissertation, I demonstrate that long-term viral persistence following infection with a neurotropic RNA virus can be reactivated, and that such recrudescence leads to a novel neuropathogenic outcome. In these studies, I characterized the persistence of MV in neurons of the CNS in immunocompetent mice and demonstrate that reactivation of viral transcription and protein synthesis is associated with a loss of adaptive immunity and the onset of severe CNS disease and motor dysfunction in mice that had presumably cleared the acute infection. The cerebellum/brain stem is the primary site of long-term maintenance of viral RNA, and loss of cell mediated viral control induces gait and motor problems consistent with cerebellar ataxia. Finally, using primary neuronal cultures I characterized the role of BST2 during neuronal viral infection and demonstrate, opposite to its well-characterized contributions in restricting viral particle release, that neuronal BST2 promotes viral spread. Together, these results show that persistent viral RNAs in the CNS are not inert, but can result in pathogenic host consequences distinct from those seen during an acute viral infection. Further, my findings underscore the cell-type specific differences of viral infection on ISG functions and immunity, highlighting the ramifications of such viral control mechanisms and their ability to promote the maintenance of viruses in the CNS that can ultimately lead to host pathogenesis.

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