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Patterns of Herpes Simplex Virus 1 Infection in Neural Progenitor Cells

作者:Wenxiao Zheng, Alissa M. Klammer, Jennifer N. Naciri, Jason Yeung, Matthew Demers, Jadranka Milošević, Paul R. Kinchington, David C. Bloom, Vishwajit L. Nimgaonkar, Leonardo D’Aiuto · 发表于:Journal of Virology · 年份:2020 · DOI:10.1128/jvi.00994-20 · 被引用次数:29 · 研究领域:Herpesvirus Infections and Treatments、Cytomegalovirus and herpesvirus research、Toxoplasma gondii Research Studies

This study employed human induced pluripotent stem cells (hiPSCs) to model the interaction of HSV-1 with NPCs, which reside in the neurogenic niches of the CNS and play a fundamental role in adult neurogenesis. Herein, we provide evidence that in NPCs infected at an MOI as low as 0.001, HSV-1 can establish a latent state, suggesting that (i) a variant of classical HSV-1 latency can be established during earlier stages of neuronal differentiation and (ii) neurogenic niches in the brain may constitute additional sites of viral reactivation. Lytic HSV-1 infections impaired NPC migration, which represents a critical step in neurogenesis. A difference in susceptibility to HSV-1 infection between two-dimensional (2D) and three-dimensional (3D) NPC cultures was observed, highlighting the potential value of 3D cultures for modeling host-pathogen interactions. Together, our results are relevant in light of observations relating HSV-1 infection to postencephalitic cognitive dysfunction.