Phosphorylated Tau's Role in Neutralizing Viral Infections

Phosphorylated tau exhibits antimicrobial activity capable of neutralizing herpes simplex virus 1 infectivity in human neurons. This research utilized a 3D human neuronal cell culture model, specifically the microglia GFP-expressing ReNcell VM neuronal cell line G10.

The culture was matured over 3.54 weeks before experiments were conducted. The study involved a triculture system combining neurons, astrocytes, and microglia, where induced pluripotent stem cells were differentiated into mature microglia over 38 days.

Following this maturation, the microglia were added to the neuronal culture and subjected to HSV-1 infection after a 24-hour incubation. After infection, the cultures underwent multiple washes and fixation with paraformaldehyde for subsequent immunostaining.

The researchers employed various antibodies to analyze p-tau levels and HSV-1 presence through confocal microscopy. The findings indicate that phosphorylated tau can significantly impact viral infectivity, suggesting a potential role in neurodegenerative disease mechanisms and therapeutic strategies.

The methodologies included viral plaque assays, viral capsid isolation, binding assays, and electron microscopy to further elucidate tau's effects on HSV-1. The study emphasizes the importance of tau in both neurobiology and virology, providing a novel perspective on its potential protective roles in the central nervous system against viral infections.

Statistical analyses were conducted using GraphPad Prism, with significance thresholds set at P < 0.05. This research underscores a critical intersection between tau pathology and viral infection dynamics in human neurons, opening up avenues for future investigations into therapeutic approaches for neurodegenerative diseases.