Dana M. Cairns, Brooke M. Smiley, Jordan A. Smiley, Yasaman Khorsandian, Marilyn Kelly, Ruth F. Itzhaki2, David L. Kaplan
Infection with herpes simplex virus type 1 (HSV-1) in the brains of APOE4 carriers increases the risk of Alzheimer’sdisease (AD). We previously found that latent HSV-1 in a three-dimensional in vitro model of APOE4- heterozygoushuman brain tissue was reactivated in response to neuroinflammation caused by exposure to other pathogens.Because traumatic brain injury also causes neuroinflammation, we surmised that brain injury might similarly reac-tivate latent HSV-1. Here, we examined the effects of one or more controlled blows to our human brain model inthe absence or presence of latent HSV-1 infection. After repeated, mild controlled blows, latently infected tissuesshowed reactivation of HSV-1; the production and accumulation of β amyloid and phosphorylated tau (whichpromotes synaptic dysfunction and neurodegeneration); and activated gliosis, which is associated with destruc-tive neuroinflammation. These effects are collectively associated with AD, dementia, and chronic traumatic en-cephalopathy (CTE) and were increased with additional injury but were absent in mock-infected tissue. Blockingthe cytokine IL-1β prevented the induction of amyloid and gliosis in latently infected monolayer cultures afterscratch wounding. We thus propose that after repeated mechanical injuries to the brain, such as from direct blowsto the head or jarring motions of the head, the resulting reactivation of HSV-1 in the brain may contribute to thedevelopment of AD and related diseases in some individuals.
Full article: https://www.science.org/doi/epdf/10.1126/scisignal.ado6430
