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

Joel A Wood; Srilakshmi Chaparala; Cecilia Bantang; Ansuman Chattopadhyay; Maribeth A Wesesky; Paul R Kinchington; Vishwajit L Nimgaonkar; David C Bloom; Leonardo D'Aiuto

doi:10.1007/s13365-024-01198-8

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

J Neurovirol. 2024 Mar 13. doi: 10.1007/s13365-024-01198-8. Online ahead of print.

Authors

Joel A Wood¹, Srilakshmi Chaparala², Cecilia Bantang¹, Ansuman Chattopadhyay², Maribeth A Wesesky¹, Paul R Kinchington³, Vishwajit L Nimgaonkar^{1

4}, David C Bloom⁵, Leonardo D'Aiuto⁶

Affiliations

¹ Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, 3811 O'Hara Street, 15213, Pittsburgh, PA, USA.
² Molecular Biology Information Service, Health Sciences Library System / Falk Library, University of Pittsburgh, M722 Alan Magee Scaife Hall / 3550 Terrace Street, 15261, Pittsburgh, PA, USA.
³ Department of Ophthalmology, University of Pittsburgh, Suite 820, Eye & Ear Building, 203 Lothrop Street, 15213, Pittsburgh, PA, USA.
⁴ VA Pittsburgh Healthcare system at U.S. Department of Veterans Affairs, Pittsburgh, PA, USA.
⁵ Academic Research Building, Department of Molecular Genetics and Microbiology, University of Florida, 1200 Newell Drive, R2-231, 32610, Gainesville, FL, USA.
⁶ Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, 3811 O'Hara Street, 15213, Pittsburgh, PA, USA. daiutol@upmc.edu.

PMID: 38478163
DOI: 10.1007/s13365-024-01198-8

Abstract

The 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.

Keywords: (hiPSCs); Herpes simplex virus (HSV); Human induced pluripotent stem cells; Neural precursor cells; Neurospheres; RNA-Seq; Time-course analysis.

Abstract

Grants and funding