Characterization of cytopathic factors through genome-wide analysis of the Zika viral proteins in fission yeast

The Zika virus (ZIKV) causes various neurologic defects including microcephaly and the Guillain-Barré syndrome. However, little is known about how ZIKV causes those diseases or which viral protein(s) is responsible for the observed cytopathic effects involved in restricted neuronal cellular growth, dysregulation of the cell cycle, and induction of cell hypertrophy or cell death. A genome-wide analysis of ZIKV proteins and peptides was conducted using fission yeast as a surrogate host. Seven ZIKV proteins conferred various cytopathic effects in which NS4A-induced cellular hypertrophy and growth restriction were mediated through the target of rapamycin (TOR) cellular stress-response pathway. These findings provide a foundation for identifying viral pathogenicity factors associated with the ZIKV diseases.

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