Laboratory of Virology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
PLoS Pathog. 2010 Jan 15;6(1):e1000730. doi: 10.1371/journal.ppat.1000730.
The porcine reproductive and respiratory syndrome virus (PRRSV) is a major threat to swine health worldwide and is considered the most significant viral disease in the swine industry today. In past years, studies on the entry of the virus into its host cell have led to the identification of a number of essential virus receptors and entry mediators. However, viral counterparts for these molecules have remained elusive and this has made rational development of new generation vaccines impossible. The main objective of this study was to identify the viral counterparts for sialoadhesin, a crucial PRRSV receptor on macrophages. For this purpose, a soluble form of sialoadhesin was constructed and validated. The soluble sialoadhesin could bind PRRSV in a sialic acid-dependent manner and could neutralize PRRSV infection of macrophages, thereby confirming the role of sialoadhesin as an essential PRRSV receptor on macrophages. Although sialic acids are present on the GP(3), GP(4) and GP(5) envelope glycoproteins, only the M/GP(5) glycoprotein complex of PRRSV was identified as a ligand for sialoadhesin. The interaction was found to be dependent on the sialic acid binding capacity of sialoadhesin and on the presence of sialic acids on GP(5). These findings not only contribute to a better understanding of PRRSV biology, but the knowledge and tools generated in this study also hold the key to the development of a new generation of PRRSV vaccines.
猪繁殖与呼吸综合征病毒（PRRSV）是全球范围内猪健康的主要威胁，被认为是当今养猪业最重要的病毒性疾病。在过去的几年中，对病毒进入宿主细胞的研究导致了一些重要的病毒受体和进入介质的鉴定。然而，这些分子的病毒对应物仍然难以捉摸，这使得新一代疫苗的合理开发成为不可能。本研究的主要目的是鉴定唾液酸黏附素的病毒对应物，这是巨噬细胞上重要的 PRRSV 受体。为此，构建并验证了唾液酸黏附素的可溶性形式。该可溶性唾液酸黏附素可以以唾液酸依赖的方式结合 PRRSV，并且可以中和 PRRSV 对巨噬细胞的感染，从而证实了唾液酸黏附素作为巨噬细胞上重要的 PRRSV 受体的作用。尽管唾液酸存在于 GP(3)、GP(4)和 GP(5)包膜糖蛋白上，但只有 PRRSV 的 M/GP(5)糖蛋白复合物被鉴定为唾液酸黏附素的配体。发现这种相互作用依赖于唾液酸黏附素的唾液酸结合能力以及 GP(5)上唾液酸的存在。这些发现不仅有助于更好地了解 PRRSV 生物学，而且本研究中获得的知识和工具也为新一代 PRRSV 疫苗的开发提供了关键。
