2. Academic Validation
  3. Human cytomegalovirus infection impairs neural differentiation via repressing sterol regulatory element binding protein 2-mediated cholesterol biosynthesis

Human cytomegalovirus infection impairs neural differentiation via repressing sterol regulatory element binding protein 2-mediated cholesterol biosynthesis

  • Cell Mol Life Sci. 2024 Jul 6;81(1):289. doi: 10.1007/s00018-024-05278-0.
Jianming Li 1,  Jingxuan Sun 1,  Mingyi Xu 1,  Lei Yang 2 3,  Ning Yang 2 3,  Jingui Deng 1 4,  Yanping Ma 1 5 6,  Ying Qi 1 5 6,  Zhongyang Liu 1 5 6,  Qiang Ruan # 7 8 9,  Yao Liu # 10 11,  Yujing Huang # 12 13 14
Affiliations

Affiliations

  • 1 Virology Laboratory, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
  • 2 Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, China.
  • 3 Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, Liaoning, China.
  • 4 Department of Microorganism Laboratory, Shenyang Center for Disease Control and Prevention, Shenyang, Liaoning, China.
  • 5 Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
  • 6 Departments of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
  • 7 Virology Laboratory, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. ruanq@sj-hospital.org.
  • 8 Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. ruanq@sj-hospital.org.
  • 9 Departments of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. ruanq@sj-hospital.org.
  • 10 Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, China. liuyao@cmu.edu.cn.
  • 11 Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, Liaoning, China. liuyao@cmu.edu.cn.
  • 12 Virology Laboratory, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. huangyj@sj-hospital.org.
  • 13 Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. huangyj@sj-hospital.org.
  • 14 Departments of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. huangyj@sj-hospital.org.
  • # Contributed equally.
PMID: 38970696 DOI: 10.1007/s00018-024-05278-0
Abstract

Congenital human cytomegalovirus (HCMV) Infection is a major cause of abnormalities and disorders in the central nervous system (CNS) and/or the peripheral nervous system (PNS). However, the complete pathogenesis of neural differentiation disorders caused by HCMV Infection remains to be fully elucidated. Stem cells from human exfoliated deciduous teeth (SHEDs) are mesenchymal stem cells (MSCs) with a high proliferation and neurogenic differentiation capacity. Since SHEDs originate from the neural crest of the early embryonic ectoderm, SHEDs were hypothesized to serve as a promising cell line for investigating the pathogenesis of neural differentiation disorders in the PNS caused by congenital HCMV Infection. In this work, SHEDs were demonstrated to be fully permissive to HCMV Infection and the virus was able to complete its life cycle in SHEDs. Under neurogenic inductive conditions, HCMV Infection of SHEDs caused an abnormal neural morphology. The expression of stem/neural cell markers was also disturbed by HCMV Infection. The impairment of neural differentiation was mainly due to a reduction of intracellular Cholesterol levels caused by HCMV Infection. Sterol regulatory element binding protein-2 (SREBP2) is a critical transcription regulator that guides Cholesterol synthesis. HCMV Infection was shown to hinder the migration of SREBP2 into nucleus and resulted in perinuclear aggregations of SREBP2 during neural differentiation. Our findings provide new insights into the prevention and treatment of nervous system diseases caused by congenital HCMV Infection.

Keywords

Cholesterol; Human cytomegalovirus; Neural differentiation; SREBP2.

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