Abstract

Background: Currently, it is unclear whether asymptomatic recurrent reactivations of herpes simplex virus type 1 (HSV-1) occur in the central nervous systems of infected people, and if these events could lead to a progressive deterioration of neuronal function. In this context, HSV-1 constitutes an important candidate to be included among the risk factors for the development of neuropathies associated with chronic neuroinflammation. Objective: The aim of this study was to assess in vivo inflammatory and neurodegenerative markers in the brain during productive and latent HSV-1 infection using a mouse model of herpes simplex encephalitis. Methods: Neuroinflammation and neurodegeneration markers were evaluated in mice trigeminal ganglia and cerebral cortex during HSV-1 infection, by immunohistochemistry, western blot, and RT-PCR. Results: Neuronal ICP4 viral antigen expression indicative of a reactivation episode during asymptomatic latency of HSV-1 infection in mice was accompanied by upregulation of neuroinflammatory (toll-like receptor-4, interferon alpha/beta, and p-IRF3) and early neurodegenerative markers (phospho-tau and TauC3). Conclusions: HSV-1 reactivation from latency induced neuroinflammatory and neurodegenerative markers in the brain of asymptomatic mice suggesting that recurrent reactivations could be associated with cumulative neuronal dysfunctions.