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Neutralizing antibodies with neurotropic factor treatment maintain neurodevelopmental gene expression upon exposure to human cytomegalovirus. J Virol 2023 Oct 31;97(10):e0069623

Date

10/05/2023

Pubmed ID

37796129

Pubmed Central ID

PMC10653813

DOI

10.1128/jvi.00696-23

Scopus ID

2-s2.0-85175819477 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

Human cytomegalovirus (HCMV) infection is the leading cause of non-heritable birth defects worldwide. HCMV readily infects the early progenitor cell population of the developing brain, and we have found that infection leads to significantly downregulated expression of key neurodevelopmental transcripts. Currently, there are no approved therapies to prevent or mitigate the effects of congenital HCMV infection. Therefore, we used human-induced pluripotent stem cell-derived organoids and neural progenitor cells to elucidate the glycoproteins and receptors used in the viral entry process and whether antibody neutralization was sufficient to block viral entry and prevent disruption of neurodevelopmental gene expression. We found that blocking viral entry alone was insufficient to maintain the expression of key neurodevelopmental genes, but neutralization combined with neurotrophic factor treatment provided robust protection. Together, these studies offer novel insight into mechanisms of HCMV infection in neural tissues, which may aid future therapeutic development.

Author List

O'Brien BS, Mokry RL, Schumacher ML, Rosas-Rogers S, Terhune SS, Ebert AD

Authors

Allison D. Ebert PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Scott Terhune PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Antibodies, Neutralizing
Cytomegalovirus
Cytomegalovirus Infections
Gene Expression
Humans
Induced Pluripotent Stem Cells
Nerve Growth Factors
Neural Stem Cells
Organoids
Receptors, Virus
Viral Envelope Proteins
Virus Internalization