Abortive infection of macrophages serves as a "dead end" for most seasonal influenza A virus (IAV) strains, and it is likely to contribute to effective host defence. Interferon (IFN)-induced transmembrane protein 3 (IFITM3) restricts the early stages of IAV replication in epithelial cells, but IFITM3 restriction of IAV replication in macrophages has not been previously investigated. Herein, macrophages isolated from IFITM3-deficient mice were more susceptible to initial IAV infection, but late-stage viral replication was still controlled through abortive infection. Strikingly, IFNα/β receptor (IFNAR)-deficient macrophages infected with IAV were not only more susceptible to initial infection, but these cells also supported productive viral replication. Significantly, we have established that abortive IAV infection in macrophages is controlled through a type I IFN-dependent mechanism, where late-stage IAV replication can proceed in the absence of type I IFN responses. These findings provide novel mechanistic insight into macrophage-specific processes that potently shut down IAV replication.

中文翻译：

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IFITM3和I型干扰素对于控制鼠巨噬细胞中的甲型流感病毒复制非常重要。

巨噬细胞的无性感染是大多数季节性A型流感病毒（IAV）菌株的“死胡同”，并且可能有助于有效的宿主防御。干扰素（IFN）诱导的跨膜蛋白3（IFITM3）限制了IAV在上皮细胞中复制的早期阶段，但是IFITM3对IAV在巨噬细胞中复制的限制尚未得到研究。在这里，从IFITM3缺陷小鼠中分离出的巨噬细胞更容易受到初始IAV感染，但后期病毒复制仍通过流产感染来控制。令人惊讶的是，IAV感染的IFNα/β受体（IFNAR）缺陷型巨噬细胞不仅更容易感染初始感染，而且这些细胞还支持有效的病毒复制。显着地，我们已经确定巨噬细胞中的流产IAV感染是通过I型IFN依赖性机制控制的，其中晚期IAV复制可以在不存在I型IFN反应的情况下进行。这些发现为巨噬细胞特定的过程提供了新颖的机制洞察力，从而有效地关闭了IAV复制。