TY - JOUR
T1 - Recurrent herpes simplex virus-1 infection induces hallmarks of neurodegeneration and cognitive deficits in mice
AU - De Chiara, Giovanna
AU - Piacentini, Roberto
AU - Fabiani, Marco
AU - Mastrodonato, Alessia
AU - Marcocci, Maria Elena
AU - Limongi, Dolores
AU - Napoletani, Giorgia
AU - Protto, Virginia
AU - Coluccio, Paolo
AU - Celestino, Ignacio
AU - Li Puma, Domenica Donatella
AU - Grassi, Claudio
AU - Palamara, Anna Teresa
PY - 2019
Y1 - 2019
N2 - Herpes simplex virus type 1 (HSV-1) is a DNA neurotropic virus, usually establishing latent infections in the trigeminal ganglia followed by periodic reactivations. Although numerous findings suggested potential links between HSV-1 and Alzheimer's disease (AD), a causal relation has not been demonstrated yet. Hence, we set up a model of recurrent HSV-1 infection in mice undergoing repeated cycles of viral reactivation. By virological and molecular analyses we found: i) HSV-1 spreading and replication in different brain regions after thermal stress-induced virus reactivations; ii) accumulation of AD hallmarks including amyloid-β protein, tau hyperphosphorylation, and neuroinflammation markers (astrogliosis, IL-1β and IL-6). Remarkably, the progressive accumulation of AD molecular biomarkers in neocortex and hippocampus of HSV-1 infected mice, triggered by repeated virus reactivations, correlated with increasing cognitive deficits becoming irreversible after seven cycles of reactivation. Collectively, our findings provide evidence that mild and recurrent HSV-1 infections in the central nervous system produce an AD-like phenotype and suggest that they are a risk factor for AD.
AB - Herpes simplex virus type 1 (HSV-1) is a DNA neurotropic virus, usually establishing latent infections in the trigeminal ganglia followed by periodic reactivations. Although numerous findings suggested potential links between HSV-1 and Alzheimer's disease (AD), a causal relation has not been demonstrated yet. Hence, we set up a model of recurrent HSV-1 infection in mice undergoing repeated cycles of viral reactivation. By virological and molecular analyses we found: i) HSV-1 spreading and replication in different brain regions after thermal stress-induced virus reactivations; ii) accumulation of AD hallmarks including amyloid-β protein, tau hyperphosphorylation, and neuroinflammation markers (astrogliosis, IL-1β and IL-6). Remarkably, the progressive accumulation of AD molecular biomarkers in neocortex and hippocampus of HSV-1 infected mice, triggered by repeated virus reactivations, correlated with increasing cognitive deficits becoming irreversible after seven cycles of reactivation. Collectively, our findings provide evidence that mild and recurrent HSV-1 infections in the central nervous system produce an AD-like phenotype and suggest that they are a risk factor for AD.
KW - Alzheimer's disease
KW - HSV-1 infected
KW - herpes simplex virus-1
KW - neurodegeneration
KW - Alzheimer's disease
KW - HSV-1 infected
KW - herpes simplex virus-1
KW - neurodegeneration
UR - http://hdl.handle.net/10807/130883
U2 - 10.1371/journal.ppat.1007617
DO - 10.1371/journal.ppat.1007617
M3 - Article
SN - 1553-7374
VL - 15
SP - N/A-N/A
JO - PLoS Pathogens
JF - PLoS Pathogens
ER -