Herpes simplex virus 1 regulates [beta]-catenin expression in TG neurons during the latency-reactivation cycle

When herpes simplex virus 1 (HSV-1) infection is initiated in the ocular, nasal, or oral cavity, sensory neurons within trigeminal ganglia (TG) become infected. Following a burst of viral transcription in TG neurons, lytic cycle viral genes are suppressed and latency is established. The latency-asso...

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Bibliographic Details
Published in:PloS one 2020-03, Vol.15 (3), p.e0230870
Main Authors: Harrison, Kelly S, Zhu, Liqian, Thunuguntla, Prasanth, Jones, Clinton, DeLuca, Neal A
Format: Article
Language:English
Subjects:
Dexamethasone
Disease transmission
Diseases
Encephalitis
Genes
Glucocorticoids
Herpes simplex
Herpes simplex virus
Herpesvirus infections
Infection
Neurons
Transcription (Genetics)
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Summary:When herpes simplex virus 1 (HSV-1) infection is initiated in the ocular, nasal, or oral cavity, sensory neurons within trigeminal ganglia (TG) become infected. Following a burst of viral transcription in TG neurons, lytic cycle viral genes are suppressed and latency is established. The latency-associated transcript (LAT) is the only viral gene abundantly expressed during latency, and LAT expression is important for the latency-reactivation cycle. Reactivation from latency is required for virus transmission and recurrent disease, including encephalitis. The Wnt/[beta]-catenin signaling pathway is differentially expressed in TG during the bovine herpesvirus 1 latency-reactivation cycle. Hence, we hypothesized HSV-1 regulates the Wnt/[beta]-catenin pathway and promotes maintenance of latency because this pathway enhances neuronal survival and axonal repair. New studies revealed [beta]-catenin was expressed in significantly more TG neurons during latency compared to TG from uninfected mice or mice latently infected with a LAT.sup.-/- mutant virus. When TG explants were incubated with media containing dexamethasone to stimulate reactivation, significantly fewer [beta]-catenin+ TG neurons were detected. Conversely, TG explants from uninfected mice or mice latently infected with a LAT.sup.-/- mutant increased the number of [beta]-catenin+ TG neurons in the presence of DEX relative to samples not treated with DEX. Impairing Wnt signaling with small molecule antagonists reduced virus shedding during explant-induced reactivation. These studies suggested [beta]-catenin was differentially expressed during the latency-reactivation cycle, in part due to LAT expression.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0230870