Herpes Simplex Virus Type 1 Induces AD-like Neurodegeneration Markers in Human Progenitor and Differentiated ReNcell VM Cells

Abstract

An increasing body of evidence strongly suggests that infections or reactivations of herpes simplex virus type 1 (HSV-1) may be closely linked to Alzheimer’s disease (AD). Promising results have been obtained using cell and animal models of HSV-1 infection, contributing to the understanding of the molecular mechanisms linking HSV-1 infection and AD neurodegeneration. ReNcell VM is a human neural stem cell line that has been used as a model system to study the impact of various infectious agents on the central nervous system. In this study, we demonstrate the suitability of the ReNcell VM cell line for developing a new in vitro model of HSV-1 infection. By following standard differentiation protocols, we were able to derive various nervous cell types, including neurons, astrocytes, and oligodendrocytes, from neural precursors. Additionally, we demonstrated the susceptibility of ReNcell VM cells, including precursor and differentiated cells, to HSV-1 infection and subsequent viral-induced AD-like neurodegeneration. Our findings support the use of this cell line to generate a new research platform for investigating AD neuropathology and its most significant risk factors, which may lead to important discoveries in the context of this highly impactful disease.

Cholesterol Modulation Attenuates the AD-Like Phenotype Induced by Herpes Simplex Virus Type 1 Infection

“…We have characterized several in vitro models using different cell lines-murine and human neuroblastoma cells and human neural precursors-where HSV-1 infection was able to induce an AD-like phenotype. This phenotype is marked by the inhibition of Aβ secretion, intracellular accumulation of Aβ and hyperphosphorylated tau protein, and alterations in autophagy-lysosomal pathway [10][11][12][13][14]. These results contribute to the growing evidence supporting the infectious hypothesis of AD and the potential role of HSV-1 in neurodegeneration, initially proposed at the end of the 20 th century [15,16].…”

Cholesterol Modulation Attenuates the AD-like Phenotype Induced by Herpes Simplex Virus Type 1 Infection

“…We have characterized several in vitro models using different cell lines-murine and human neuroblastoma cells and human neural precursors-where AD hallmarks were reported upon HSV-1 infection. This phenotype includes the inhibition of Aβ secretion, intracellular accumulation of Aβ and hyperphosphorylated tau protein, and alterations in the autophagy-lysosomal pathway [10][11][12][13][14]. These results contribute to the growing evidence supporting the infectious hypothesis of AD and the potential role of HSV-1 in neurodegeneration, initially proposed at the end of the 20th century [15,16].…”