Cytomegalovirus infection lengthens the cell cycle of granule cell precursors during postnatal cerebellar development

Cathy Yea Won Sung; Mao Li; Stipan Jonjic; Veronica Sanchez; William J Britt

doi:10.1172/jci.insight.175525

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Cytomegalovirus infection lengthens the cell cycle of granule cell precursors during postnatal cerebellar development

Journal article

Open access

Peer reviewed

Cytomegalovirus infection lengthens the cell cycle of granule cell precursors during postnatal cerebellar development

Cathy Yea Won Sung, Mao Li, Stipan Jonjic, Veronica Sanchez and William J Britt

JCI insight, Vol.9(11), e175525

06/10/2024

DOI: 10.1172/jci.insight.175525

PMCID: PMC11382886

PMID: 38855871

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https://doi.org/10.1172/jci.insight.175525View

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Abstract

Human cytomegalovirus (HCMV) infection in infants infected in utero can lead to a variety of neurodevelopmental disorders. However, mechanisms underlying altered neurodevelopment in infected infants remain poorly understood. We have previously described a murine model of congenital HCMV infection in which murine CMV (MCMV) spreads hematogenously and establishes a focal infection in all regions of the brain of newborn mice, including the cerebellum. Infection resulted in disruption of cerebellar cortical development characterized by reduced cerebellar size and foliation. This disruption was associated with altered cell cycle progression of the granule cell precursors (GCPs), which are the progenitors that give rise to granule cells (GCs), the most abundant neurons in the cerebellum. In the current study, we have demonstrated that MCMV infection leads to prolonged GCP cell cycle, premature exit from the cell cycle, and reduced numbers of GCs resulting in cerebellar hypoplasia. Treatment with TNF-α neutralizing antibody partially normalized the cell cycle alterations of GCPs and altered cerebellar morphogenesis induced by MCMV infection. Collectively, our results argue that virus-induced inflammation altered the cell cycle of GCPs resulting in a reduced numbers of GCs and cerebellar cortical hypoplasia, thus providing a potential mechanism for altered neurodevelopment in fetuses infected with HCMV.

Animals

Animals, Newborn

Cell Cycle

Cerebellum - abnormalities

Cerebellum - growth & development

Cerebellum - pathology

Cerebellum - virology

Cytomegalovirus

Cytomegalovirus Infections - pathology

Cytomegalovirus Infections - virology

Developmental Disabilities

Disease Models, Animal

Female

Humans

Mice

Muromegalovirus - physiology

Nervous System Malformations

Neural Stem Cells - virology

Neurons - virology

Tumor Necrosis Factor-alpha - metabolism

Details

Title: Subtitle: Cytomegalovirus infection lengthens the cell cycle of granule cell precursors during postnatal cerebellar development
Creators: Cathy Yea Won Sung - University of Alabama at Birmingham
Mao Li - University of Alabama at Birmingham
Stipan Jonjic - University of Rijeka
Veronica Sanchez - University of Alabama at Birmingham
William J Britt - University of Alabama at Birmingham
Resource Type: Journal article
Publication Details: JCI insight, Vol.9(11), e175525
DOI: 10.1172/jci.insight.175525
PMID: 38855871
PMCID: PMC11382886
NLM abbreviation: JCI Insight
ISSN: 2379-3708
eISSN: 2379-3708
Language: English
Date published: 06/10/2024
Academic Unit: Biology
Record Identifier: 9984961046702771

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