Rubella virus tropism and single-cell responses in human primary tissue and microglia-containing organoids

Author:

Popova Galina12345ORCID,Retallack Hanna6ORCID,Kim Chang N12345,Wang Albert12345ORCID,Shin David12345,DeRisi Joseph L67,Nowakowski Tomasz12345ORCID

Affiliation:

1. Department of Neurological Surgery, University of California, San Francisco

2. Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco

3. Department of Anatomy, University of California, San Francisco

4. Department of Psychiatry and Behavioral Sciences, University of California, San Francisco

5. Weill Institute for Neurosciences, University of California, San Francisco

6. Department of Biochemistry and Biophysics, University of California, San Francisco

7. Chan Zuckerberg Biohub

Abstract

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.

Funder

National Institutes of Health

Simons Foundation

Chan Zuckerberg Biohub

NARSAD

Schmidt Futures

William K. Bowes, Jr. Foundation

University of California, San Francisco

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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