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Human cytomegalovirus induces significant structural and functional changes in terminally differentiated human cortical neurons. mBio 2023 Nov 15;14(6):e0225123

Date

11/15/2023

Pubmed ID

37966250

Pubmed Central ID

PMC10746155

DOI

10.1128/mbio.02251-23

Scopus ID

2-s2.0-85183165409 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

Human cytomegalovirus (HCMV) is a highly prevalent viral pathogen that can cause serious neurological deficits in infants experiencing an in utero infection. Also, as a life-long infection, HCMV has been associated with several diseases in the adult brain. HCMV is known to infect early neural progenitor cells, but whether it also infects terminally differentiated neurons is still debated. Here, we differentiated human-induced pluripotent stem cells into neurons for 84-120 days to test the ability of HCMV to infect terminally differentiated neurons and assess the downstream functional consequences. We discovered that mature human neurons are highly permissive to HCMV infection, exhibited late replication hallmarks, and produced infectious virus. Moreover, infection in terminally differentiated neurons essentially eliminated neuron function. These results demonstrate that terminally differentiated human neurons are permissive to HCMV infection, which can significantly alter both structural and functional features of this mature neuron population.

Author List

Adelman JW, Rosas-Rogers S, Schumacher ML, Mokry RL, 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