找到"罪魁祸首"？华人科学家首次锁定寨卡病毒内致病蛋白
找到"罪魁祸首"？华人科学家首次锁定寨卡病毒内致病蛋白【财新网】（记者 苑苏文）科学家对寨卡病毒致病原理的研究终于取得突破。美国马里兰大学医学院的科学家首次锁定了寨卡病毒内的7个潜在的致病性关键蛋白。该项研究首次全面描述了寨卡病毒基因组，并于近日在《美国国家科学院院刊》上发表。 今年初，寨卡病毒在南美洲爆发，并向全球蔓延，导致小头畸形在内的出生缺陷和神经系统疾病，甚至危及生命。 世界卫生组织2016年12月30日发布公报称，自2015年5月巴西出现寨卡病毒传播以来，美洲48个国家和地区报告了53.2万例寨卡病毒感染病例，其中17.5万例为确诊病例。此外，该地区22个国家和地区报告了2400余例与寨卡病毒感染相关的先天性综合征。 该项研究的首席研究员，马里兰大学医学院里学教授赵玉琪（Richard Zhao）指出，这项研究结果能帮助人们了解寨卡病毒如何影响细胞，从而为未来的研究提供方向。 赵玉琪团队使用裂殖酵母分析寨卡病毒，这种酵母起源自非洲，用于酿造啤酒。目前，这种酵母已经成为检测病原体如何影响细胞的常见模型生物，也被用来研究可导致艾滋病的HIV病毒、大麦黄矮病毒等。 研究人员从完整的寨卡病毒中分离出来14种病毒蛋白质和小分子多肽，然后让他们和裂殖酵母细胞接触，观察对细胞的影响。最终，14种蛋白中7种能抑制酵母细胞的生长，或将其杀死。下一步，研究人员将继续观察这7中致病蛋白在大鼠和人体细胞内的作用。 赵玉琪是文革后首批经高考进入大学的77级大学生，也是中美建交后中国向美国派出的第一批计划内留学生，现为美国马里兰大学医学院病理系、微生物-免疫学系及人类病毒研究所终身教授。在中国，他身兼中国预防性病艾滋病基金会顾问等职位，并与中国高校合作培养多名博士和硕士研究生。
Characterization of cytopathic factors through genome-wide analysis of the Zika viral proteins in fission yeast
Ge Lia, Melissa Poulsena, Csaba Fenyvuesvolgyia, Yoko Yashirodab, Minoru Yoshidab, J. Marc Simarda,c, Robert C. Gallod,e,f,1, and Richard Y. Zhao
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.
http://www.pnas.org/content/early/2017/01/01/1619735114.abstract?sid=55190fc8-48d6-4aaf-9517-8eb0bcd0af27 新突破 :):):):):):):) :):) :):):handshake
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