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- W2937126669 abstract "Herpes simplex virus 1 (HSV-1) establishes lifelong latent infections in neurons. Reactivation from latency can lead to serious recurrent disease, including stromal keratitis, corneal scarring, blindness, and encephalitis. Although numerous studies link stress to an increase in the incidence of reactivation from latency and recurrent disease, the mechanism of action is not well understood. We hypothesized that stress, via corticosteroid-mediated activation of the glucocorticoid receptor (GR), stimulates viral gene expression and productive infection during reactivation from latency. Consequently, we tested whether GR activation by the synthetic corticosteroid dexamethasone influenced virus shedding during reactivation from latency using trigeminal ganglion (TG) explants from Swiss Webster mice latently infected with HSV-1, strain McKrae. TG explants from the latently infected mice shed significantly higher levels of virus when treated with dexamethasone. Conversely, virus shedding from TG explants was significantly impaired when they were incubated with medium containing a GR-specific antagonist (CORT-108297) or stripped fetal bovine serum, which lacks nuclear hormones and other growth factors. TG explants from latently infected, but not uninfected, TG contained significantly more GR-positive neurons following explant when treated with dexamethasone. Strikingly, VP16 protein expression was detected in TG neurons at 8 hours after explant whereas infected-cell protein 0 (ICP0) and ICP4 protein expression was not readily detected until 16 hours after explant. Expression of all three viral regulatory proteins was stimulated by dexamethasone. These studies indicated corticosteroid-mediated GR activation increased the number of TG neurons expressing viral regulatory proteins, which enhanced virus shedding during explant-induced reactivation from latency.IMPORTANCE Herpes simplex virus 1 (HSV-1) establishes lifelong latent infections in neurons within trigeminal ganglia (TG); periodically, reactivation from latency occurs, leading to virus transmission and recurrent disease. Chronic or acute stress increases the frequency of reactivation from latency; how this occurs is not well understood. Here, we demonstrate that the synthetic corticosteroid dexamethasone stimulated explant-induced reactivation from latency. Conversely, a glucocorticoid receptor (GR) antagonist significantly impaired reactivation from latency, indicating that GR activation stimulated explant-induced reactivation. The viral regulatory protein VP16 was readily detected in TG neurons prior to infected-cell protein 0 (ICP0) and ICP4 during explant-induced reactivation. Dexamethasone induced expression of all three viral regulatory proteins following TG explant. Whereas the immunosuppressive properties of corticosteroids would facilitate viral spread during reactivation from latency, these studies indicate GR activation increases the number of TG neurons that express viral regulatory proteins during early stages of explant-induced reactivation." @default.
- W2937126669 created "2019-04-25" @default.
- W2937126669 creator A5020518181 @default.
- W2937126669 creator A5035845710 @default.
- W2937126669 creator A5051702258 @default.
- W2937126669 creator A5052608133 @default.
- W2937126669 date "2019-07-01" @default.
- W2937126669 modified "2023-09-26" @default.
- W2937126669 title "Antagonizing the Glucocorticoid Receptor Impairs Explant-Induced Reactivation in Mice Latently Infected with Herpes Simplex Virus 1" @default.
- W2937126669 cites W1223737510 @default.
- W2937126669 cites W1543912722 @default.
- W2937126669 cites W1745264954 @default.
- W2937126669 cites W1761323037 @default.
- W2937126669 cites W1806240087 @default.
- W2937126669 cites W1817074176 @default.
- W2937126669 cites W1899539978 @default.
- W2937126669 cites W1900646268 @default.
- W2937126669 cites W1923807735 @default.
- W2937126669 cites W1963759306 @default.
- W2937126669 cites W1963903389 @default.
- W2937126669 cites W1968643495 @default.
- W2937126669 cites W1970023609 @default.
- W2937126669 cites W1971552605 @default.
- W2937126669 cites W1973602401 @default.
- W2937126669 cites W197844582 @default.
- W2937126669 cites W1979772713 @default.
- W2937126669 cites W1980305746 @default.
- W2937126669 cites W1988030420 @default.
- W2937126669 cites W1988999154 @default.
- W2937126669 cites W1991010205 @default.
- W2937126669 cites W1991520255 @default.
- W2937126669 cites W1992339013 @default.
- W2937126669 cites W1995796039 @default.
- W2937126669 cites W1997624180 @default.
- W2937126669 cites W1998086294 @default.
- W2937126669 cites W1998527359 @default.
- W2937126669 cites W1998817848 @default.
- W2937126669 cites W1999740789 @default.
- W2937126669 cites W2001476460 @default.
- W2937126669 cites W2005358378 @default.
- W2937126669 cites W2006485530 @default.
- W2937126669 cites W2010254493 @default.
- W2937126669 cites W2011299553 @default.
- W2937126669 cites W2012588421 @default.
- W2937126669 cites W2015438051 @default.
- W2937126669 cites W2028165101 @default.
- W2937126669 cites W2042268096 @default.
- W2937126669 cites W2042714171 @default.
- W2937126669 cites W2043756403 @default.
- W2937126669 cites W2043796750 @default.
- W2937126669 cites W2046489321 @default.
- W2937126669 cites W2049110705 @default.
- W2937126669 cites W205363467 @default.
- W2937126669 cites W2055203668 @default.
- W2937126669 cites W2055666727 @default.
- W2937126669 cites W2056295530 @default.
- W2937126669 cites W2058071990 @default.
- W2937126669 cites W2060047331 @default.
- W2937126669 cites W2064479381 @default.
- W2937126669 cites W2068246413 @default.
- W2937126669 cites W2072300954 @default.
- W2937126669 cites W2075007419 @default.
- W2937126669 cites W2079543085 @default.
- W2937126669 cites W2079885319 @default.
- W2937126669 cites W2080846870 @default.
- W2937126669 cites W2084133551 @default.
- W2937126669 cites W2089034029 @default.
- W2937126669 cites W2094419454 @default.
- W2937126669 cites W2099303824 @default.
- W2937126669 cites W2099460378 @default.
- W2937126669 cites W2101269168 @default.
- W2937126669 cites W2101899737 @default.
- W2937126669 cites W2102152711 @default.
- W2937126669 cites W2102636938 @default.
- W2937126669 cites W2102762115 @default.
- W2937126669 cites W2104560888 @default.
- W2937126669 cites W2111770560 @default.
- W2937126669 cites W2112265428 @default.
- W2937126669 cites W2118749448 @default.
- W2937126669 cites W2118882782 @default.
- W2937126669 cites W2122097157 @default.
- W2937126669 cites W2125161768 @default.
- W2937126669 cites W2126134216 @default.
- W2937126669 cites W2127846162 @default.
- W2937126669 cites W2128177613 @default.
- W2937126669 cites W2128569914 @default.
- W2937126669 cites W2129129906 @default.
- W2937126669 cites W2129972061 @default.
- W2937126669 cites W2139798327 @default.
- W2937126669 cites W2141955811 @default.
- W2937126669 cites W2142082591 @default.
- W2937126669 cites W2142536229 @default.
- W2937126669 cites W2143001268 @default.
- W2937126669 cites W2144091055 @default.
- W2937126669 cites W2150691073 @default.
- W2937126669 cites W2151938173 @default.
- W2937126669 cites W2152908311 @default.
- W2937126669 cites W2160927412 @default.
- W2937126669 cites W2161508569 @default.
- W2937126669 cites W2162751422 @default.