Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China.
Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, China.
Vet Microbiol. 2022 Feb;265:109315. doi: 10.1016/j.vetmic.2021.109315. Epub 2021 Dec 24.
Porcine hemagglutinating encephalomyelitis virus (PHEV) is a neurotropic coronavirus and highly pathogenic in veterinary clinic. Spike (S) protein of PHEV interplays with host components to cross the plasma membrane of target cells, but characterization of its functional receptors is limited. Here, we discovered that cell-surface glycans, i.e., sialic acid (SA) and heparan sulfate (HS), act as critical interacting factors of PHEV, involving in viral attachment. As shown in glycans depletion assay, removing SA or HS from N2a cells inhibits PHEV infection. Soluble sugar monomers were utilized for competitive binding tests, and we found that both SA and HS could specifically bind to PHEV and affect the viral infectivity. Furthermore, the expression of heparan sulfate proteoglycans (HSPGs), including syndecans and glypicans, and endoglycosidase heparinase which cleaves HS were regulated by PHEV RNA replication. Together, we newly identified specificity recognition of cellular glycans and PHEV during infection, providing novel cellular targets for antiviral therapies and better understanding of pathogenesis.
猪传染性脑脊髓炎病毒（PHEV）是一种神经嗜性冠状病毒，在兽医临床中具有高度致病性。PHEV 的刺突（S）蛋白与宿主成分相互作用，穿过靶细胞的质膜，但对其功能性受体的特征描述有限。在这里，我们发现细胞表面糖，即唾液酸（SA）和硫酸乙酰肝素（HS），作为 PHEV 的关键相互作用因子，参与病毒附着。如糖耗尽实验所示，从 N2a 细胞中去除 SA 或 HS 会抑制 PHEV 感染。利用可溶性糖单体进行竞争结合试验，我们发现 SA 和 HS 均可特异性结合 PHEV 并影响病毒感染力。此外，包括 syndecans 和 glypicans 在内的硫酸乙酰肝素蛋白聚糖（HSPGs）的表达以及切割 HS 的内切糖苷酶肝素酶均受 PHEV RNA 复制调控。总的来说，我们新发现了细胞糖和 PHEV 在感染过程中的特异性识别，为抗病毒治疗提供了新的细胞靶点，并更好地理解了发病机制。
