Neuroinflammation is associated with reduced SOCS2 and SOCS3 expression during intracranial HSV-1 infection.

Neuroscience letters 2020 Sep 25

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Herpes simplex virus type 1 (HSV-1) is the main etiological agent of acute and sporadic encephalitis. Proteins of the suppressor of cytokine signaling (SOCS) family have shown to regulate the inflammation during HSV-1 infection in the brain. However, the effects of SOCS2 and SOCS3 in viral encephalitis remain unclear. The aim of the current study is to investigate the potential association between SOCS2, SOCS3, cytokines, and hippocampal damage, especially neuronal apoptosis, during acute intracranial HSV-1 infection in mice. Male C57BL/6 mice were infected by intracranial route with 102 plaque-forming units (PFU) inoculum of purified HSV-1. At three days post-infection (3 d.p.i.), mice were euthanized and their hippocampi were collected for histopathological analysis, immunohistochemical reaction against active caspase-3 and quantification of SOCS2, SOCS3 and cytokines (tumoral necrosis factor (TNF), interleukin (IL) 1β, IL-6, IL-10; interferon (IFN) -α, IFN-β, IFN-γ) mRNA expression. Infected mice exhibited neuronal loss and hemorrhagic focus in Cornu Ammonis (CA) region. The apoptotic index was higher in infected mice compared to controls. HSV-1 infection was associated with increased hippocampal expression of TNF, IL1-β, IL-6 and IFNα/IFNβ and decreased expression of IL-10, IFN-γ, SOCS2 and SOCS3. Our results suggest that down regulation of SOCS2 and SOCS3 contributes to a pro-inflammatory environment associated with hippocampal damage and neuronal apoptosis during acute HSV-1 infection in mice. Copyright © 2020 Elsevier B.V. All rights reserved.

Citation

Eliana Cristina de Brito Toscano, Larissa Fonseca da Cunha Sousa, Graciela Kunrath Lima, Leonardo Antunes Mesquita, Márcia Carvalho Vilela, David Henrique Rodrigues, Rodrigo Novaes Ferreira, Frederico Marianetti Soriani, Marco Antônio Campos, Erna Geessien Kroon, Mauro Martins Teixeira, Aline Silva de Miranda, Milene Alvarenga Rachid, Antônio Lúcio Teixeira. Neuroinflammation is associated with reduced SOCS2 and SOCS3 expression during intracranial HSV-1 infection. Neuroscience letters. 2020 Sep 25;736:135295