HSV-1 TRIGGERS ALZHEIMER-LIKE NEURODEGENERATIVE MARKERS IN GLIAL CELLS: A PROTECTIVE ROLE FOR LACTOFERRIN

Growing evidence implicates Herpes simplex virus type 1 (HSV1) as a contributing factor in Alzheimer’s disease (AD) pathogenesis. While most studies have focused on neuronal susceptibility, the role of glial cells in HSV1‑driven neurodegenerative mechanisms remains insufficiently explored. This study investigated whether HSV
1 infection induces AD‑like alterations in murine glial cultures and evaluated the neuroprotective potential of lactoferrin, an iron‑binding glycoprotein with antiviral properties. Primary murine oligodendrocyte precursor cell cultures containing astrocytes were differentiated into mature oligodendrocytes and infected with HSV1. Viral replication and infectivity were quantified by western blot, qPCR, and plaque assays. AD‑related markers—including amyloid‑β (Aβ) accumulation, Aβ secretion, and tau phosphorylation—were assessed by immunofluorescence, immunoblotting, and ELISA assays. The impact of lactoferrin on viral infection and neurodegenerative signatures was evaluated in both oligodendrocytes and astrocytes. HSV1 efficiently infected glial cultures, completing a productive lytic cycle and inducing hallmark AD‑like alterations: intracellular Aβ accumulation, reduced Aβ secretion, and tau hyperphosphorylation. Lactoferrin markedly inhibited HSV1 entry and replication, reducing viral DNA and protein levels. Importantly, lactoferrin prevented HSV1‑induced Aβ accumulation and tau hyperphosphorylation, restoring a non‑pathological phenotype in infected glial cells. These findings indicate that glial cells actively contribute to HSV1‑mediated neurodegenerative processes and identify lactoferrin as a potent antiviral and neuroprotective candidate capable of mitigating AD‑like pathology. Overall, this work highlights glial cells as active players in virus‑associated neurodegeneration and supports further in vivo and translational studies to assess lactoferrin’s therapeutic potential.