RNA-Seq time-course analysis of neural precursor cell transcriptome in response to herpes simplex Virus-1 infection

Author:

Wood Joel A.,Chaparala Srilakshmi,Bantang Cecilia,Chattopadhyay Ansuman,Wesesky Maribeth A.,Kinchington Paul R.,Nimgaonkar Vishwajit L.,Bloom David C.,D’Aiuto LeonardoORCID

Abstract

AbstractThe neurogenic niches within the central nervous system serve as essential reservoirs for neural precursor cells (NPCs), playing a crucial role in neurogenesis. However, these NPCs are particularly vulnerable to infection by the herpes simplex virus 1 (HSV-1). In the present study, we investigated the changes in the transcriptome of NPCs in response to HSV-1 infection using bulk RNA-Seq, compared to those of uninfected samples, at different time points post infection and in the presence or absence of antivirals. The results showed that NPCs upon HSV-1 infection undergo a significant dysregulation of genes playing a crucial role in aspects of neurogenesis, including genes affecting NPC proliferation, migration, and differentiation. Our analysis revealed that the CREB signaling, which plays a crucial role in the regulation of neurogenesis and memory consolidation, was the most consistantly downregulated pathway, even in the presence of antivirals. Additionally, cholesterol biosynthesis was significantly downregulated in HSV-1-infected NPCs. The findings from this study, for the first time, offer insights into the intricate molecular mechanisms that underlie the neurogenesis impairment associated with HSV-1 infection.

Funder

NINDS

NIAID

NEI

NIMH

SMRI

Publisher

Springer Science and Business Media LLC

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