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Impact of a cytomegalovirus kinase inhibitor on infection and neuronal progenitor cell differentiation. Antiviral Res 2016 May;129:67-73

Date

02/16/2016

Pubmed ID

26875788

Pubmed Central ID

PMC4957402

DOI

10.1016/j.antiviral.2016.02.007

Scopus ID

2-s2.0-84959527703   5 Citations

Abstract

Human cytomegalovirus (HCMV) is the leading cause of congenital infections. Symptomatic newborns present with a range of sequelae including disorders of the CNS such as visual impairment, microcephaly, mental retardation and hearing loss. HCMV congenital infection causes gross changes in brain morphology and disturbances in glial and neuronal distribution, number and migration. In these studies, we have evaluated the effectiveness of the antiviral maribavir in inhibiting HCMV infections of ES cell-derived neuronal progenitor cells (NPC). We used EZ-spheres generated from H9 ES cells which are pre-rosette NPCs that retain long-term potential to differentiate into diverse central and peripheral neural lineages following directed differentiation. Our results demonstrate that the maribavir disrupts HCMV replication and viral yield in undifferentiated EZ-sphere-derived NPCs. In addition, we observed that maribavir limits HCMV replication and reduces the percentage of infected cells during differentiation of NPCs. Finally, early steps in differentiation are maintained during infection by treating with maribavir, likely an indirect effect resulting from decreased viral spread. Future studies of NPC proliferation and differentiation during infection treated with maribavir could provide the impetus for studying maribavir as an antiviral agent for congenital HCMV disease.

Author List

Bigley TM, McGivern JV, Ebert AD, Terhune SS

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

Antiviral Agents
Benzimidazoles
Cell Line
Embryonic Stem Cells
Humans
Neural Stem Cells
Neurogenesis
Neurons
Ribonucleosides
Virus Replication