Sawtell Lab

  • Current Projects

    Our projects focus on different aspects of herpes simplex virus (HSV) disease from a molecular perspective. We are exploring how VP16, the viral transactivator of lytic gene expression, is turned on from the latent viral genome. Also, we are investigating the role of Trim19 (PML) nuclear body formation in silencing the HSV genome in sensory neurons. Our work also includes the identification of host genes conferring susceptibility and resistance to HSV disease using a forward genetic approach.

    Our lab also studies the role of IL10 in modulating the accrual of central nervous system (CNS) lesions during long-term HSV latency / reactivation cycles. IL10 plays a pivotal role in curtailing the inflammatory responses and thus balances resolution and pathogenic outcome.

    To date, the importance of IL10 during long-term repeated reactivation cycles within the CNS has not been reported. Utilizing mice deficient in IL10, we tested the hypothesis that IL10 plays a critical role in limiting reactive damage within the nervous system during latent infection.

    Our findings suggest HSV latency in the CNS has the potential, in a susceptible host background, to mediate a silent progressive development of CNS pathology. This has significant implications for neurological disorders in an aging population.

 
  • Post-translational regulation of key viral transactivators in ganglion neurons.

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    Post-translational regulation of key viral transactivators in ganglion neurons.

    HSV promoter reporter mutants combined with immunohistochemical detection of viral proteins reveal post-translational regulation of key viral transactivators in ganglion neurons.

  • Reactive glial cells.

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    Reactive glial cells.

    Immunohistochemical detection of glial fibrillary associated protein in brains  harboring latent viral genomes reveals reactive glial cells (A) that progress and increase in number over time (B).

  • Stress induced changes lead to reactivation in rare neurons.

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    Stress induced changes lead to reactivation in rare neurons.
    Summary of timing and frequency of HSV reactivation in vivo.