Mannose binding lectin (MBL) generally plays a protective role during viral infection, yet MBL-mediated complement activation promotes Ross River virus (RRV)-induced inflammatory tissue destruction, contributing to arthritis and myositis. As MBL binds to carbohydrates, we hypothesized that N-linked glycans on the RRV envelope glycoproteins act as ligands for MBL. Using a panel of RRV mutants lacking the envelope N-linked glycans, we found that MBL deposition onto infected cells was dependent on the E2 glycans. Moreover, the glycan-deficient viruses exhibited reduced disease and tissue damage in a mouse model of RRV-induced myositis compared to wild-type RRV, despite similar viral load and inflammatory infiltrates within the skeletal muscle. Instead, the reduced disease induced by glycan-deficient viruses was linked to decreased MBL deposition and complement activation within inflamed tissues. These results demonstrate that the viral N-linked glycans promote MBL deposition and complement activation onto RRV-infected cells, contributing to the development of RRV-induced myositis.

甘露糖结合凝集素 (MBL) 通常在病毒感染期间起保护作用，但 MBL 介导的补体激活会促进罗斯河病毒 (RRV) 诱导的炎症组织破坏，从而导致关节炎和肌炎。由于 MBL 与碳水化合物结合，我们假设 RRV 包膜糖蛋白上的 N 连接聚糖充当 MBL 的配体。使用一组缺乏包膜 N 连接聚糖的 RRV 突变体，我们发现 MBL 在受感染细胞上的沉积依赖于 E2 聚糖。此外，与野生型 RRV 相比，尽管在骨骼肌内的病毒载量和炎症浸润相似，但在 RRV 诱导的肌炎小鼠模型中，聚糖缺陷病毒表现出减少的疾病和组织损伤。反而，聚糖缺陷病毒诱导的疾病减少与炎症组织内 MBL 沉积和补体激活减少有关。这些结果表明，病毒 N-连接聚糖促进 MBL 沉积和补体激活到 RRV 感染的细胞上，从而促进 RRV 诱导的肌炎的发展。