Child Health, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, United Kingdom.
Computational Chemistry, Chemistry, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, United Kingdom.
J Innate Immun. 2019;11(1):13-28. doi: 10.1159/000492974. Epub 2018 Oct 5.
Innate recognition of viruses is an essential part of the immune response to viral pathogens. This is integral to the maintenance of healthy lungs, which are free from infection and efficient at gaseous exchange. An important component of innate immunity for identifying viruses is the family of C-type collagen-containing lectins, also known as collectins. These secreted, soluble proteins are pattern recognition receptors (PRRs) which recognise pathogen-associated molecular patterns (PAMPs), including viral glycoproteins. These innate immune proteins are composed of trimerized units which oligomerise into higher-order structures and facilitate the clearance of viral pathogens through multiple mechanisms. Similarly, many viral surface proteins form trimeric configurations, despite not showing primary protein sequence similarities across the virus classes and families to which they belong. In this review, we discuss the role of the lung collectins, i.e., surfactant proteins A and D (SP-A and SP-D) in viral recognition. We focus particularly on the structural similarity and complementarity of these trimeric collectins with the trimeric viral fusion proteins with which, we hypothesise, they have elegantly co-evolved. Recombinant versions of these innate immune proteins may have therapeutic potential in a range of infectious and inflammatory lung diseases including anti-viral therapeutics.
先天识别病毒是对病毒病原体免疫反应的重要组成部分。这对于维持健康的肺部至关重要，肺部没有感染，气体交换效率高。识别病毒的先天免疫的一个重要组成部分是含有 C 型胶原蛋白的凝集素家族，也称为 collectins。这些分泌的可溶性蛋白质是模式识别受体 (PRR)，可识别病原体相关的分子模式 (PAMP)，包括病毒糖蛋白。这些先天免疫蛋白由三聚体单元组成，这些三聚体单元寡聚形成更高阶的结构，并通过多种机制促进清除病毒病原体。同样，许多病毒表面蛋白形成三聚体构象，尽管它们在所属的病毒类和科之间没有显示出主要的蛋白质序列相似性。在这篇综述中，我们讨论了肺 collectins（即表面活性剂蛋白 A 和 D (SP-A 和 SP-D)）在病毒识别中的作用。我们特别关注这些三聚体 collectins 与三聚体病毒融合蛋白的结构相似性和互补性，我们假设它们与这些融合蛋白优雅地共同进化。这些先天免疫蛋白的重组版本可能在一系列感染和炎症性肺部疾病中具有治疗潜力，包括抗病毒治疗。
