Resolution of herpes simplex virus reactivation in vivo results in neuronal destruction

PLoS Pathogens
Jessica R DollN M Sawtell

Abstract

A fundamental question in herpes simplex virus (HSV) pathogenesis is the consequence of viral reactivation to the neuron. Evidence supporting both post-reactivation survival and demise is published. The exceedingly rare nature of this event at the neuronal level in the sensory ganglion has limited direct examination of this important question. In this study, an in-depth in vivo analysis of the resolution of reactivation was undertaken. Latently infected C57BL/6 mice were induced to reactivate in vivo by hyperthermic stress. Infectious virus was detected in a high percentage (60-80%) of the trigeminal ganglia from these mice at 20 hours post-reactivation stimulus, but declined by 48 hours post-stimulus (0-13%). With increasing time post-reactivation stimulus, the percentage of reactivating neurons surrounded by a cellular cuff increased, which correlated with a decrease in detectable infectious virus and number of viral protein positive neurons. Importantly, in addition to intact viral protein positive neurons, fragmented viral protein positive neurons morphologically consistent with apoptotic bodies and containing cleaved caspase-3 were detected. The frequency of this phenotype increased through time post-reactivation. These fr...Continue Reading

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Citations

Jul 28, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Janardan P PandeyHugo Lövheim
Oct 20, 2020·Journal of Alzheimer's Disease : JAD·Michael R DugganKamel Khalili
Feb 27, 2021·Current Opinion in Virology·Ilena Vincenti, Doron Merkler
May 20, 2021·American Journal of Clinical Dermatology·Theodora K Karagounis, Miriam K Pomeranz
Aug 28, 2021·Frontiers in Cellular Neuroscience·Sujata PrasadJames R Lokensgard

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Methods Mentioned

BETA
flow cytometry
biopsies
PCR

Software Mentioned

FlowJo
GraphPad Prism
GraphPad

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