Herpes Simplex Virus-Type1 (HSV-1) Impairs DNA Repair in Cortical Neurons.
Several findings suggest that Herpes simplex virus-1 (HSV-1) infection plays a role in the neurodegenerative processes that characterize Alzheimer's disease (AD), but the underlying mechanisms have yet to be fully elucidated. Here we show that HSV-1 productive infection in cortical neurons causes the accumulation of DNA lesions that include both single (SSBs) and double strand breaks (DSBs), which are reported to be implicated in the neuronal loss observed in neurodegenerative diseases. We demonstrate that HSV-1 downregulates the expression level of Ku80, one of the main components of non-homologous end joining (NHEJ), a major pathway for the repair of DSBs. We also provide data suggesting that HSV-1 drives Ku80 for proteasomal degradation and impairs NHEJ activity, leading to DSB accumulation. Since HSV-1 usually causes life-long recurrent infections, it is possible to speculate that cumulating damages, including those occurring on DNA, may contribute to virus induced neurotoxicity and neurodegeneration, further suggesting HSV-1 as a risk factor for neurodegenerative conditions.
Department of Cell Biology and Neuroscience, Istituto Superiore di SanitàRome, Italy; Institute of Translational Pharmacology, National Research CouncilRome, Italy.
Giovanna
G
De Chiara
Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità Rome, Italy.
Mauro
M
Racaniello
Department of Cell Biology and Neuroscience, Istituto Superiore di SanitàRome, Italy; Institute of Translational Pharmacology, National Research CouncilRome, Italy.
Cristiana
C
Mollinari
Department of Public Health and Infectious Diseases, Sapienza University of Rome Rome, Italy.
Maria Elena
ME
Marcocci
Laboratory of Biosafety and Risk Assessment, Division of Health Technologies, Department of Sustainable Territorial and Production Systems, ENEA Casaccia Research Center Rome, Italy.
Giorgia
G
Aversa
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana Rome, Italy.
Alessio
A
Cardinale
Laboratory of Biosafety and Risk Assessment, Division of Health Technologies, Department of Sustainable Territorial and Production Systems, ENEA Casaccia Research Center Rome, Italy.
Anna
A
Giovanetti
Telematic University San Raffaele Rome, Italy.
Enrico
E
Garaci
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele PisanaRome, Italy; Department of Public Health and Infectious Diseases, Institute Pasteur Cenci Bolognetti Foundation, Sapienza University of RomeRome, Italy.
Anna Teresa
AT
Palamara
Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità Rome, Italy.
Daniela
D
Merlo
Alzheimer’s disease; DNA damage; DSBs; HSV-1; Ku80