College of Veterinary Medicine, Northwest A&F University, Yangling, Xianyang 712100, China.
Chinese Academy of Medical Sciences, Changchun Institute of Veterinary Medicine, Changchun 130122, China.
Viruses. 2022 Oct 30;14(11):2407. doi: 10.3390/v14112407.
Rotavirus (RV) is a non-enveloped icosahedral virus with an 11-segment double-stranded RNA genome, belonging to the family of rotaviruses. RV is one of the pathogens causing diarrhea in infants and young animals, and it induces the production of type I interferons (IFNs), which can trigger antiviral function by inducing the production of interferon-stimulated genes (ISGs). Although IFITM3, an ISG localizing to late endosomes, can limit many viral infections, whether or not it restricts the infection of RV is still unknown. Therefore, we attempted to determine whether IFITM3 also restricts RV infection by using over-expression and knockout cell strains. It was found that IFITM3-expressing cell strains were less susceptible to RV infection, as the replication of RV in over-expressing cells was significantly less than in control group cells. Correspondingly, IFITM3-knockout cells were significantly susceptible compared to the normal cells. Furthermore, the IFN-induced antiviral effect was significantly attenuated in the absence of IFITM3, and IFITM3 delayed RV escape from endosomes in the presence of IFITM3, suggesting that endogenous IFITM3 is of great importance in type I IFN-mediated antiviral responses and may restrict infection by affecting the function of the late endosomal compartment. In conclusion, these data provide the first evidence that IFITM3 limits RV infection in vitro and delays RV escape from late endosomes into the cytoplasm.
轮状病毒（RV）是一种无包膜的二十面体病毒，具有 11 个片段的双链 RNA 基因组，属于轮状病毒科。RV 是引起婴儿和幼小动物腹泻的病原体之一，它诱导 I 型干扰素（IFNs）的产生，通过诱导干扰素刺激基因（ISGs）的产生来触发抗病毒功能。虽然定位在内体晚期的 ISG IFITM3 可以限制许多病毒感染，但它是否限制 RV 的感染尚不清楚。因此，我们试图通过使用过表达和敲除细胞株来确定 IFITM3 是否也限制 RV 感染。结果发现，IFITM3 表达细胞株对 RV 感染的敏感性降低，因为 RV 在过表达细胞中的复制明显少于对照组细胞。相应地，与正常细胞相比，IFITM3 敲除细胞明显易感。此外，在缺乏 IFITM3 的情况下，IFN 诱导的抗病毒作用显著减弱，而 IFITM3 在存在 IFITM3 的情况下延迟 RV 从内体逃逸，表明内源性 IFITM3 在 I 型 IFN 介导的抗病毒反应中非常重要，可能通过影响晚期内体区室的功能来限制感染。总之，这些数据首次提供了证据表明 IFITM3 限制了 RV 在体外的感染，并延迟了 RV 从晚期内体逃逸到细胞质。
