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J.M. Hill, D.M. Neumann, D.T. Stark, L. Kodi, P.S. Bhattacharjee, H.W. Thompson, D.C. Bloom; Butyrate Induces Ocular HSV–1 Shedding and Neuronal Reactivation in Mouse and Rabbit Eye Models . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2802.
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Purpose.To determine if systemic administration of sodium butyrate, a known histone deacetylase inhibitor, induces HSV–1 ocular and neuronal reactivation in mice and rabbits latent with HSV–1. Methods: Mice (BALB/c females) were latently infected with HSV–1 strain McKrae (LAT+) or the LAT–negative control (dLAT2903). Rabbits (NZ white) were latently infected with HSV–1 strains McKrae or 17Syn+. Sodium butyrate (1.2 g/kg) was administered i.p. daily to mice on post inoculation (PI) days 28 and 29; eyes were swabbed on PI days 29 and 30 and trigeminal ganglia (TG) were obtained on day 30. Rabbits received butyrate in their drinking water (0.1%) and via daily i.p. injections (0.1 g/kg) for 22 days beginning on PI day 21; eyes were swabbed daily for 22 days beginning on day 21. Control rabbits received PBS. Results: Sodium butyrate–treated mice latent with McKrae (LAT+) showed high rates of reactivation (∼100%) as measured by the presence of infectious virus in tears and TG. Mice latent with HSV–1 recombinant dLAT2903 (LAT–) showed no reactivation. Rabbits treated with sodium butyrate had a significantly higher frequency of HSV–1 shedding (∼2–fold) and significantly more shedding episodes (∼2–fold) as measured by HSV–positive ocular swabs, compared with the PBS–treated rabbits. Conclusions: Butyrate induced HSV–1 reactivation in mice and rabbits latent with HSV–1 strains McKrae and 17Syn+. Our hypothesis is that LAT+ HSV–1 strains that are known to reactivate by adrenergic induction or immunosuppression will also reactivate when treated with butyrate. It is possible that chromatin remodeling augmented by the administration of butyrate is the mechanism of action of this drug in these animal models.
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