Jaime L. Wetzel

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Toll-like receptors (TLRs) recognize specific microbial products and elicit innate immune signals to activate specific transcription factors that induce protective proteins, such as interferon. TLR3 is localized to endosomes and recognizes double-stranded RNA (dsRNA), which is generated by virally infected or apoptotic cells. TLR3 has been genetically(More)
Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54(More)
Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders that are characterized by progressive spasticity of the lower extremities, due to axonal degeneration in the corticospinal motor tracts. HSPs are genetically heterogeneous and show autosomal dominant inheritance in ∼70-80% of cases, with additional cases being recessive or(More)
The transcription factor IRF-3 mediates cellular antiviral response by inducing the expression of interferon and other antiviral proteins. In RNA-virus infected cells, IRF-3's transcriptional activation is triggered primarily by RIG-I-like receptors (RLR), which can also activate the RLR-induced IRF-3-mediated pathway of apoptosis (RIPA). Here, we have(More)
Interferon (IFN) is required for protecting mice from viral pathogenesis; reciprocally, it mediates the deleterious septic shock response to bacterial infection. The critical transcription factor for IFN induction, in both cases, is IRF-3, which is activated by TLR3 or RIG-I signaling in response to virus infection and TLR4 signaling in response to(More)
UNLABELLED The type I/III interferon (IFN) system has major roles in regulating viral pathogenesis, usually ameliorating pathogenesis by impairing virus replication through the antiviral actions of one or more IFN-induced proteins. Ifit2 is one such protein which can be induced by IFN or virus infection, and it is responsible for protecting mice from(More)
UNLABELLED The interferon system provides the first line of host defense against virus infection. Mouse pathogenesis studies have revealed the importance of specific interferon-induced proteins in providing protection against specific viruses. We have previously reported that one such protein, Ifit2, protects neurons of the central nervous system from(More)
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