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Integrative systems biology characterizes immune-mediated neurodevelopmental changes in murine Zika Virus microcephaly

ABSTRACT: A new mouse model for congenital Zika infection in a wildtype, immunocompetent background employing intraplacental infection resulted in productive infection of embryonic brains and features of microcephaly during early development (E10.5-16.5). Gross morphological characterization showed translational relevance for understanding the viral neuropathogenesis and Zika-associated microcephaly in humans. Thus, an integrated, multi-omics (RNA-sequencing, proteomics) analysis of fetal brain tissues was performed to understand pathways perturbed by viral infection in developing brains. These analyses identified virus-induced defects in cell cycle progression and neurodevelopment, in S-phase DNA replication and NEUROD2/TBR2 transcription factor cascades, respectively. Among the most significant responses was induction of innate immune programs in ZIKV-infected brains, including immunoproteasome activation and MHC-I antigen display associated with immune cell infiltration and neuronal death during early development. Identification of specific components within major pathways contributing to viral infection-induced effects on neurodevelopment provides novel targets for therapeutic intervention against neurotropic infections and ZIKV-associated microcephaly specifically.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Judith A. Steen

PROVIDER: MSV000091415 | MassIVE | Mon Mar 06 08:28:00 GMT 2023

SECONDARY ACCESSION(S): PXD040624

REPOSITORIES: MassIVE

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