After primary infection, herpes simplex virus type 1 (HSV-1) can reach the central nervous system and, in rare cases, cause herpes simplex encephalitis (HSE). The HSV-1 genome has also been detected in the brains of individuals without clinical symptoms, and markers of viral reactivation have been linked to a higher risk of developing Alzheimer’s disease (AD). Experimental studies suggest that recurrent HSV-1 reactivation activates neurotoxic pathways and promotes AD-like pathology, but the underlying mechanisms remain unresolved.

We aim to investigate whether HSV-1 infection or latency-associated transcript (LAT) expression promotes tunneling nanotube (TNT) formation and intercellular communication in neurons. We will also determine the relative contribution of viral latency versus productive infection to TNT formation, cell-to-cell spread, and protein aggregation. Finally, we will assess whether increased TNT formation facilitates the propagation of misfolded proteins to uninfected neurons, thereby contributing to AD pathology.

To address these questions, we have established two complementary experimental platforms: a reporter system that enables visualization and quantification of neuronal cell-cell communication, and a protocol to establish latency with controlled HSV-1 reactivation. Together, these tools will allow us to dissect the role of HSV-1 in TNT-mediated intercellular spread and its potential contribution to neurodegeneration.