Department of Biological Sciences, National University of Singapore, Singapore, Singapore.
Department of Biochemistry, National University of Singapore, Singapore, Singapore.
Protein Sci. 2023 Oct;32(10):e4761. doi: 10.1002/pro.4761.
The pupal cuticle protein from Aedes aegypti (AaPC) inhibits dengue virus (DENV) infection; however, the underlying mechanism of this inhibition remains unknown. Here, we report that AaPC is an intrinsically disordered protein and interacts with domain I/II of the DENV envelope protein via residues Asp59, Asp61, Glu71, Asp73, Ser75, and Asp80. AaPC can directly bind to and cause the aggregation of DENV, which in turn blocks virus infection during the virus-cell fusion stage. AaPC may also influence viral recognition and attachment by interacting with human immune receptors DC-SIGN and CD4. These findings enhance our understanding of the role of AaPC in mitigating viral infection and suggest that AaPC is a potential target for developing inhibitors or antibodies to control dengue virus infection.
埃及伊蚊蛹壳蛋白（AaPC）抑制登革热病毒（DENV）感染；然而，这种抑制的潜在机制尚不清楚。在这里，我们报告 AaPC 是一种固有无序蛋白，并通过残基 Asp59、Asp61、Glu71、Asp73、Ser75 和 Asp80 与 DENV 包膜蛋白的结构域 I/II 相互作用。AaPC 可以直接结合并导致 DENV 聚集，从而在病毒-细胞融合阶段阻止病毒感染。AaPC 还可以通过与人类免疫受体 DC-SIGN 和 CD4 相互作用来影响病毒的识别和附着。这些发现增强了我们对 AaPC 在减轻病毒感染中的作用的理解，并表明 AaPC 是开发抑制剂或抗体来控制登革热病毒感染的潜在靶点。
