Lo Yen-Lung, Liou Gunn-Guang, Lyu Jia-Huei, Hsiao Michael, Hsu Tsui-Ling, Wong Chi-Huey
Genomics Research Center, Academia Sinica, Taipei, Taiwan.
Chemical Biology and Molecular Biophysics, Taiwan International Graduate Program, Academia Sinica, Taipei, Taiwan.
PLoS One. 2016 Nov 10;11(11):e0166474. doi: 10.1371/journal.pone.0166474. eCollection 2016.
Dengue fever is a mosquito-borne viral pandemic disease that is widespread in the tropical and subtropical areas. Dengue virus uses human mannose-binding receptor (MR) and DC-SIGN on macrophages as primary receptors, and CLEC5A as signaling receptor to sense the dengue virus invasion and then to signal and stimulate macrophages to secrete cytokines. But the interplay between MR/DC-SIGN and CLEC5A is unknown. Here we demonstrate a plausible mechanism for the interaction, i.e. MR/DC-SIGN first attracts the virus with high avidity, and the virus concurrently interacts with CLEC5A in close proximity to form a multivalent hetero-complex and facilitate CLEC5A-mediated signal transduction. Our study suggests that the cooperation between a high-avidity lectin-virus interaction and a nearby low-avidity signaling receptor provides a necessary connection between binding and signaling. Understanding this mechanism may lead to the development of a new antiviral strategy.
登革热是一种由蚊子传播的病毒性大流行疾病，在热带和亚热带地区广泛传播。登革病毒将人类甘露糖结合受体（MR）和巨噬细胞上的DC-SIGN作为主要受体，并将C型凝集素结构域家族5成员A（CLEC5A）作为信号受体，以感知登革病毒的入侵，然后发出信号并刺激巨噬细胞分泌细胞因子。但MR/DC-SIGN与CLEC5A之间的相互作用尚不清楚。在此，我们展示了一种可能的相互作用机制，即MR/DC-SIGN首先以高亲和力吸引病毒，同时病毒与附近的CLEC5A相互作用形成多价异源复合物，促进CLEC5A介导的信号转导。我们的研究表明，高亲和力凝集素-病毒相互作用与附近低亲和力信号受体之间的协同作用为结合与信号传导提供了必要的联系。了解这一机制可能会促成新的抗病毒策略的开发。
