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

Area of Science:

• Neuroscience
• Virology
• Genomics

Background:

• Congenital Zika virus (ZIKV) infection poses a significant threat to fetal neurodevelopment.
• Understanding the molecular mechanisms underlying ZIKV-induced brain abnormalities is crucial for therapeutic development.

Purpose of the Study:

• To characterize the molecular pathway perturbations in the embryonic brain following congenital ZIKV infection.
• To identify key genes and proteins affected by ZIKV infection that contribute to microcephaly.

Main Methods:

• Integrative systems biology approach combining proteomics and RNA-sequencing.
• Analysis of embryonic brain tissues from a wild-type, immunocompetent mouse model of congenital ZIKV infection.

Main Results:

• ZIKV infection triggered a strong immune response and downregulated critical neurodevelopmental gene programs.
• A negative correlation was observed between ZIKV polyprotein levels and host cell cycle proteins.
• Downregulation of microcephaly-associated genes/proteins, such as Eomesodermin/T-box Brain Protein 2 (EOMES/TBR2) and Neuronal Differentiation 2 (NEUROD2), was identified.

Conclusions:

• Molecular pathway disturbances in neural progenitors and neurons contribute to the complex brain phenotype of congenital ZIKV infection.
• This study provides insights into the ZIKV immunopathological landscape and fetal immune response in the developing brain at the protein and transcript levels.