Modeling Aβ42 Accumulation in Response to Herpes Simplex Virus 1 Infection: Two Dimensional or Three Dimensional?

作者：Eric E. Abrahamson, Wenxiao Zheng, Vaishali Muralidaran, Miloš D. Ikonomović, David C. Bloom, Vishwajit L. Nimgaonkar, Leonardo D’Aiuto · 发表于：Journal of Virology · 年份：2020 · DOI：10.1128/jvi.02219-20 · 被引用次数：36 · 研究领域：Alzheimer's disease research and treatments、Tryptophan and brain disorders、Prion Diseases and Protein Misfolding

The "pathogen" hypothesis of Alzheimer's disease (AD) proposes that brain HSV-1 infection could be an initial source of amyloid beta (Aβ) peptide-containing amyloid plaque development. Aβ accumulation was reported in HSV-1-infected 2D neuronal cultures and neural stem cell cultures, as well as in HSV-1-infected 3D neuronal culture models.The current study extends these findings by showing different patterns of Aβ42 accumulation following HSV-1 infection of 2D compared to 3D neuronal cultures (brain organoids). Specifically, 2D neuronal cultures showed Aβ42-immunoreactivity mainly in HSV-1-infected cells and only rarely in uninfected cells or infected cells exposed to antivirals. Conversely, 3D brain organoids showed accumulation of Aβ42 mainly in non-infected cells surrounding HSV-1-infected cells. We suggest that because brain organoids better recapitulate architectural features of a developing brain than 2D cultures, they may be a more suitable model to investigate the involvement of HSV-1 in the onset of AD pathology.