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

• DOI: 10.1016/j.isci.2023.106909
• Publication Date: 2023-05-19T07:59:35Z
• Authors: Kimino Fujimura; Amanda J. Guise; Tojo Nakayama; Christoph N. Schl...; Anais Meziani; Mukesh Kumar; Long Cheng; Dylan J. Vaughan; Andrew Kodani; Simon Van Haren; Kenneth Parker; Ofer Levy; Ann F. Durbin; Irene Bosch; Lee Gehrke; Hanno Steen; Ganeshwaran H. Mo...; Judith A. Steen
• Keywords: Zika Virus; Microcephaly

Characterizing perturbation of molecular pathways in congenital Zika virus (ZIKV) infection is critical for improved therapeutic approaches. Leveraging integrative systems biology, proteomics, and RNA-seq, we analyzed embryonic brain tissues from an immunocompetent, wild-type ZIKV mouse model. induced a robust immune response accompanied by the downregulation neurodevelopmental gene programs. We identified negative correlation between polyprotein abundance host cell cycle-inducing proteins. further captured genes/proteins, many which are known to be causative human microcephaly, including Eomesodermin/T-box Brain Protein 2 (EOMES/TBR2) Neuronal Differentiation (NEUROD2). Disturbances distinct neural progenitors post-mitotic neurons may contribute complex phenotype infection. Overall, this report on protein- transcript-level dynamics enhances understanding immunopathological landscape through characterization fetal developing brain.