VIB Center for Brain and Disease Research, Leuven, Belgium.
Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Nat Commun. 2020 Jun 5;11(1):2832. doi: 10.1038/s41467-020-16721-8.
Human amyloids have been shown to interact with viruses and interfere with viral replication. Based on this observation, we employed a synthetic biology approach in which we engineered virus-specific amyloids against influenza A and Zika proteins. Each amyloid shares a homologous aggregation-prone fragment with a specific viral target protein. For influenza we demonstrate that a designer amyloid against PB2 accumulates in influenza A-infected tissue in vivo. Moreover, this amyloid acts specifically against influenza A and its common PB2 polymorphisms, but not influenza B, which lacks the homologous fragment. Our model amyloid demonstrates that the sequence specificity of amyloid interactions has the capacity to tune amyloid-virus interactions while allowing for the flexibility to maintain activity on evolutionary diverging variants.
已经有研究表明，人类淀粉样蛋白可以与病毒相互作用并干扰病毒复制。基于这一观察结果，我们采用了一种合成生物学方法，针对甲型流感和寨卡病毒蛋白设计了具有病毒特异性的淀粉样蛋白。每个淀粉样蛋白都与特定病毒靶蛋白共享同源的聚集倾向片段。对于流感，我们证明了针对 PB2 的设计淀粉样蛋白在体内会积累在感染流感病毒的组织中。此外，这种淀粉样蛋白特异性地针对甲型流感及其常见的 PB2 多态性，而不是缺乏同源片段的乙型流感。我们的模型淀粉样蛋白表明，淀粉样蛋白相互作用的序列特异性具有调节淀粉样蛋白-病毒相互作用的能力，同时允许在进化上有差异的变体中保持活性的灵活性。
