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

Autor:	Fujimura K; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.; Division of Genetics and Genomics and The Manton Center for Orphan Disease, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA.; Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.; Department of Pediatrics, Shin-Yurigaoka General Hospital, Kanagawa, Japan., Guise AJ; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Nakayama T; Division of Genetics and Genomics and The Manton Center for Orphan Disease, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA., Schlaffner CN; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Meziani A; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Kumar M; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Cheng L; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Vaughan DJ; Division of Genetics and Genomics and The Manton Center for Orphan Disease, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA., Kodani A; Center for Pediatric Neurological Disease Research and Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Van Haren S; Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA., Parker K; SimulTOF Systems, Marlborough, MA, USA., Levy O; Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA.; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA., Durbin AF; Department of Microbiology, Harvard Medical School, Boston, MA, USA.; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA., Bosch I; Department of Microbiology, Harvard Medical School, Boston, MA, USA.; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA., Gehrke L; Department of Microbiology, Harvard Medical School, Boston, MA, USA.; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA., Steen H; Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA.; Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Mochida GH; Division of Genetics and Genomics and The Manton Center for Orphan Disease, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA.; Pediatric Neurology Unit, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA., Steen JA; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2023 May 19; Vol. 26 (7), pp. 106909. Date of Electronic Publication: 2023 May 19 (Print Publication: 2023).
DOI:	10.1016/j.isci.2023.106909
Abstrakt:	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 congenital ZIKV infection mouse model. ZIKV induced a robust immune response accompanied by the downregulation of critical neurodevelopmental gene programs. We identified a negative correlation between ZIKV polyprotein abundance and host cell cycle-inducing proteins. We further captured the downregulation of genes/proteins, many of which are known to be causative for human microcephaly, including Eomesodermin/T-box Brain Protein 2 (EOMES/TBR2) and Neuronal Differentiation 2 (NEUROD2). Disturbances of distinct molecular pathways in neural progenitors and post-mitotic neurons may contribute to complex brain phenotype of congenital ZIKV infection. Overall, this report on protein- and transcript-level dynamics enhances understanding of the ZIKV immunopathological landscape through characterization of fetal immune response in the developing brain. Competing Interests: The authors declare no conflicts of interest. (© 2023.)
Databáze:	MEDLINE
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