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D.A. Leib, J.L. Prior, J. Song, G.D. Luker; Real-Time Imaging of HSV-1 Tropism and Spread . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4630.
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Purpose: Viruses which express luciferase reporter genes can be detected in living mice with bioluminescence imaging, enabling the real time monitoring of growth and spread of HSV infections in a variety of tissues including eyes, footpads, brains and spinal cords. The goal of this study was to determine if this methodology could be employed to investigate alterations in HSV tropism and spread in the presence or absence of type I and type II interferon (IFN) receptors. Methods: A recombinant virus (termed KOSDlux) that expresses firefly luciferase under control of the ICP8 promoter was used to infect wild type mice (strain129 Ev/Sv) or congenic mice lacking IFNαß, IFNγ or IFNαßγ receptors via the footpads. Mice were injected with luciferin and imaged daily for 7 days postinfection using a Xenogen in vivo imaging system (IVIS). Using region-of-interest analysis, relative intensities of transmitted light were quantified for the feet, spinal cords and brains. Results: In the feet of wild-type infected mice, light intensity reached a peak on day 3, slowly returned close to baseline by day 6 but sometimes rebounded on days 7 and 10, possibly representing zosteriform spread. There was low activity in the spinal cord on days 1 and 2, and no activity detectable in the brain. IFNαß and IFNγ receptor-deficient mice showed a similar distribution of bioluminescence, although relative luciferase activity in spine and feet on days 1-3 postinfection showed the rank order of IFNαß > IFNγ > wild-type. In stark contrast to all other strains, IFNαßγ mice had significantly higher levels of luciferase activity in feet and spinal cords, with high brain activity preceding death on day 4. Conclusions: Real-time bioluminescent imaging can be used to study the tropism and spread of HSV-1 in the nervous system. In the absence of IFNαß receptors, IFNγ is a critical factor in protecting the nervous system from HSV-1 infection and encephalitis.
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