{Reference Type}: Journal Article
{Title}: Herpes simplex virus 1 accelerates the progression of Alzheimer's disease by modulating microglial phagocytosis and activating NLRP3 pathway.
{Author}: Wang Z;Liu J;Han J;Zhang T;Li S;Hou Y;Su H;Han F;Zhang C;
{Journal}: J Neuroinflammation
{Volume}: 21
{Issue}: 1
{Year}: 2024 Jul 18
{Factor}: 9.587
{DOI}: 10.1186/s12974-024-03166-9
{Abstract}: Accumulating evidence implicates that herpes simplex virus type 1 (HSV-1) has been linked to the development and progression of Alzheimer's disease (AD). HSV-1 infection induces β-amyloid (Aβ) deposition in vitro and in vivo, but the effect and precise mechanism remain elusive. Here, we show that HSV-1 infection of the brains of transgenic 5xFAD mice resulted in accelerated Aβ deposition, gliosis, and cognitive dysfunction. We demonstrate that HSV-1 infection induced the recruitment of microglia to the viral core to trigger microglial phagocytosis of HSV-GFP-positive neuronal cells. In addition, we reveal that the NLRP3 inflammasome pathway induced by HSV-1 infection played a crucial role in Aβ deposition and the progression of AD caused by HSV-1 infection. Blockade of the NLRP3 inflammasome signaling reduces Aβ deposition and alleviates cognitive decline in 5xFAD mice after HSV-1 infection. Our findings support the notion that HSV-1 infection is a key factor in the etiology of AD, demonstrating that NLRP3 inflammasome activation functions in the interface of HSV-1 infection and Aβ deposition in AD.