Herpes simplex virus type 1 (HSV-1) is a DNA neurotropic virus, usually establishing latentinfections in the trigeminal ganglia followed by periodic reactivations. Although numerousfindings suggested potential links between HSV-1 and Alzheimer’s disease (AD), a causalrelation has not been demonstrated yet. Hence, we set up a model of recurrent HSV-1 infectionin mice undergoing repeated cycles of viral reactivation. By virological and molecularanalyses we found: i) HSV-1 spreading and replication in different brain regions after thermalstress-induced virus reactivations; ii) accumulation of AD hallmarks including amyloid-βprotein, tau hyperphosphorylation, and neuroinflammation markers (astrogliosis, IL-1β andIL-6). Remarkably, the progressive accumulation of AD molecular biomarkers in neocortexand hippocampus of HSV-1 infected mice, triggered by repeated virus reactivations, correlatedwith increasing cognitive deficits becoming irreversible after seven cycles of reactivation.Collectively, our findings provide evidence that mild and recurrent HSV-1 infections inthe central nervous system produce an AD-like phenotype and suggest that they are a riskfactor for AD.

Recurrent herpes simplex virus-1 infection induces hallmarks of neurodegeneration and cognitive deficits in mice

Limongi D;
2019-01-01

Abstract

Herpes simplex virus type 1 (HSV-1) is a DNA neurotropic virus, usually establishing latentinfections in the trigeminal ganglia followed by periodic reactivations. Although numerousfindings suggested potential links between HSV-1 and Alzheimer’s disease (AD), a causalrelation has not been demonstrated yet. Hence, we set up a model of recurrent HSV-1 infectionin mice undergoing repeated cycles of viral reactivation. By virological and molecularanalyses we found: i) HSV-1 spreading and replication in different brain regions after thermalstress-induced virus reactivations; ii) accumulation of AD hallmarks including amyloid-βprotein, tau hyperphosphorylation, and neuroinflammation markers (astrogliosis, IL-1β andIL-6). Remarkably, the progressive accumulation of AD molecular biomarkers in neocortexand hippocampus of HSV-1 infected mice, triggered by repeated virus reactivations, correlatedwith increasing cognitive deficits becoming irreversible after seven cycles of reactivation.Collectively, our findings provide evidence that mild and recurrent HSV-1 infections inthe central nervous system produce an AD-like phenotype and suggest that they are a riskfactor for AD.
2019
HSV1; neurodegeneration
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12078/3332
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