PNAS:科学家首次鉴别出让寨卡病毒如此致命的关键蛋白

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

当寨卡病毒横空出世时科学家们对其知之甚少。在过去一年里研究者们通过深入研究来阐明寨卡病毒为何会引发一系列危险的健康问题。包括新生儿缺陷等，比如小头畸型和神经性问题（格--巴二氏综合征等）。但研究者们并不知道寨卡病毒哪种蛋白会让其变得具有杀伤性。当然他们也不清楚这些蛋白质的作用机理是什么。

The Zika virus (ZIKV) causes microcephaly and the Guillain-Barré syndrome. Little is known about how ZIKV causes these conditions or which ZIKV viral protein(s) is responsible for the associated ZIKV-induced cytopathic effects, including cell hypertrophy, growth restriction, cell-cycle dysregulation, and cell death. We used fission yeast for the rapid, global functional analysis of the ZIKV genome. All 14 proteins or small peptides were produced under an inducible promoter, and we measured the intracellular localization and the specific effects on ZIKV-associated cytopathic activities of each protein. The subcellular localization of each ZIKV protein was in overall agreement with its predicted protein structure. Five structural and two nonstructural ZIKV proteins showed various levels of cytopathic effects. The expression of these ZIKV proteins restricted cell proliferation, induced hypertrophy, or triggered cellular oxidative stress leading to cell death. The expression of premembrane protein (prM) resulted in cell-cycle G1 accumulation, whereas membrane-anchored capsid (anaC), membrane protein (M), envelope protein (E), and nonstructural protein 4A (NS4A) caused cell-cycle G2/M accumulation. A mechanistic study revealed that NS4A-induced cellular hypertrophy and growth restriction were mediated specifically through the target of rapamycin (TOR) cellular stress pathway involving Tor1 and type 2A phosphatase activator Tip41. These findings should provide a reference for future research on the prevention and treatment of ZIKV diseases.