TY - JOUR
T1 - Herpes simplex virus-type1 (HSV-1) impairs DNA repair in cortical neurons
AU - De Chiara, Giovanna
AU - Racaniello, Mauro
AU - Mollinari, Cristiana
AU - Marcocci, Maria Elena
AU - Aversa, Giorgia
AU - Cardinale, Alessio
AU - Giovanetti, Anna
AU - Garaci, Enrico
AU - Palamara, Anna Teresa
AU - Merlo, Daniela
PY - 2016/10/18
Y1 - 2016/10/18
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - DNA damage
KW - DSBs
KW - HSV-1
KW - Ku80
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UR - http://www.scopus.com/inward/citedby.url?scp=84997078017&partnerID=8YFLogxK
U2 - 10.3389/fnagi.2016.00242
DO - 10.3389/fnagi.2016.00242
M3 - Article
AN - SCOPUS:84997078017
VL - 8
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
SN - 1663-4365
IS - OCT
M1 - 242
ER -