Structure of the zebrafish galectin-1-L2 and model of its interaction with the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein
Structure of the zebrafish galectin-1-L2 and model of its interaction with the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein
复制标题
DOI：
10.1093/glycob/cwz015
复制
发表时间：
2019-05-01
期刊：
影响因子：
4.3
通讯作者：
Bianchet, Mario A.
中科院分区：
文献类型：
--
作者：
Ghosh, Anita;Banerjee, Aditi;Bianchet, Mario A.
Galectins是高度保守的β-半乳糖苷结合凝集素，在发育和免疫动态平衡中具有多种调节作用，并在微生物感染过程中发挥保护作用。近年来，Galectins在病毒感染中的作用引起了人们的极大兴趣。对高致病性病毒的研究为Galectins参与病毒感染的不同阶段提供了宝贵的见解，包括附着和进入。这些进程的详细机制和结构方面仍未确定。为了解决这些知识上的一些空白，我们以斑马鱼为模型系统，研究了半乳糖凝集素在传染性造血坏死病毒(IHNV)感染中的作用。IHNV是一种横纹病毒，导致养殖和野生鲑鱼的重大损失。与其他横纹病病毒一样，IHNV的特征是由糖蛋白的三聚体组成，显示多个N-连接的寡糖，并通过介导病毒的附着和融合在病毒感染中发挥不可或缺的作用。斑马鱼的原生典型Galectin Drgal1-L2和嵌合型Galectin Drgal3-L1直接与IHNV糖基化的包膜相互作用，显著减少病毒附着。在本研究中，我们报道了在2.0埃分辨率下，Drgal1-L2与N-乙酰-D-乳糖胺的络合物的结构。为了从结构上深入了解这些Galectin对IHNV与斑马鱼上皮细胞附着的抑制作用，我们基于人Galectin-3以及IHNV糖蛋白的胞外结构域对Drgal3-L1进行了建模。这些模型表明，这些Galectin与IHNV糖蛋白的结合以不同的强度阻碍了感染所需的病毒附着。
Galectins, highly conserved beta-galactoside-binding lectins, have diverse regulatory roles in development and immune homeostasis and can mediate protective functions during microbial infection. In recent years, the role of galectins in viral infection has generated considerable interest. Studies on highly pathogenic viruses have provided invaluable insight into the participation of galectins in various stages of viral infection, including attachment and entry. Detailed mechanistic and structural aspects of these processes remain undetermined. To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish. Like other rhabdoviruses, IHNV is characterized by an envelope consisting of trimers of a glycoprotein that display multiple N-linked oligosaccharides and play an integral role in viral infection by mediating the virus attachment and fusion. Zebrafish's proto-typical galectin Drgal1-L2 and the chimeric-type galectin Drgal3-L1 interact directly with the glycosylated envelope of IHNV, and significantly reduce viral attachment. In this study, we report the structure of the complex of Drgal1-L2 with N-acetyl-D-lactosamine at 2.0 angstrom resolution. To gain structural insight into the inhibitory effect of these galectins on IHNV attachment to the zebrafish epithelial cells, we modeled Drgal3-L1 based on human galectin-3, as well as, the ectodomain of the IHNV glycoprotein. These models suggest mechanisms for which the binding of these galectins to the IHNV glycoprotein hinders with different potencies the viral attachment required for infection.