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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
