Rubella virus tropism and single-cell responses in human primary tissue and microglia-containing organoids.
brain organoid
development
human
neuroscience
regenerative medicine
stem cells
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
20 07 2023
20 07 2023
Historique:
medline:
21
7
2023
pubmed:
20
7
2023
entrez:
20
7
2023
Statut:
epublish
Résumé
Rubella virus is an important human pathogen that can cause neurological deficits in a developing fetus when contracted during pregnancy. Despite successful vaccination programs in the Americas and many developed countries, rubella remains endemic in many regions worldwide and outbreaks occur wherever population immunity is insufficient. Intense interest since rubella virus was first isolated in 1962 has advanced our understanding of clinical outcomes after infection disrupts key processes of fetal neurodevelopment. Yet it is still largely unknown which cell types in the developing brain are targeted. We show that in human brain slices, rubella virus predominantly infects microglia. This infection occurs in a heterogeneous population but not in a highly microglia-enriched monoculture in the absence of other cell types. By using an organoid-microglia model, we further demonstrate that rubella virus infection leads to a profound interferon response in non-microglial cells, including neurons and neural progenitor cells, and this response is attenuated by the presence of microglia.
Identifiants
pubmed: 37470786
doi: 10.7554/eLife.87696
pii: 87696
pmc: PMC10370260
doi:
pii:
Banques de données
GEO
['GSE232462']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM141323
Pays : United States
Organisme : NIH HHS
ID : 5F31NS108615
Pays : United States
Organisme : NIH HHS
ID : R01NS123263
Pays : United States
Organisme : NIH HHS
ID : 1F32MH118785
Pays : United States
Informations de copyright
© 2023, Popova, Retallack et al.
Déclaration de conflit d'intérêts
GP, HR, CK, AW, DS, JD, TN No competing interests declared
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