Cytopathic effects of Zika virus proteins

Zika virus (ZIKV) can cause microcephaly in newborn children and Guillain-Barré syndrome in adults, but the precise viral proteins that trigger the cellular changes underlying these conditions remain unknown.

Using fission yeast engineered to produce the 14 proteins and peptides encoded by the ZIKV genome, researchers examined the proteins’ cellular localization and effects under controlled conditions.

All ZIKV proteins containing a membrane-associated domain were localized in the endoplasmic reticulum network, a cellular conveyor system involved in protein sorting. Seven of the 14 proteins limited cell growth and division, induced cell enlargement, disrupted the cell cycle, triggered oxidative stress responses, and spurred cell death.

The pathologic effects were comparable to those seen in ZIKV-infected mouse and human neuronal cells. Further, analysis of the mechanism of action of the NS4A protein revealed that cell enlargement and growth restriction were likely induced by engaging a cellular stress response mechanism orchestrated by the protein TOR1 upon oxidative stress, nitrogen deficiency, and flaviviral infections.

Similarly, the E protein, found on the viral surface and implicated in establishing human infection, triggered yeast cell death.

Validating the pathologic effects of ZIKV proteins in mammalian cells might aid the development of drug targets and vaccines against human infection, according to the authors.

http://www.pnas.org/content/early/2017/01/01/1619735114