Rabies virus (RABV) infection can initiate the host immune defence response and induce an antiviral state characterized by the expression of interferon (IFN)-stimulated genes (ISGs), among which the family of genes of IFN-induced protein with tetratricopeptide repeats (Ifits) are prominent representatives. Herein, we demonstrated that the mRNA and protein levels of Ifit1, Ifit2 and Ifit3 were highly increased in cultured cells and mouse brains after RABV infection. Recombinant RABV expressing Ifit3, designated rRABV-Ifit3, displayed a lower pathogenicity than the parent RABV in C57BL/6 mice after intramuscular administration, and Ifit3-deficient mice exhibited higher susceptibility to RABV infection and higher mortality during RABV infection. Moreover, compared with their individual expressions, co-expression of Ifit2 and Ifit3 could more effectively inhibit RABV replication in vitro. These results indicate that murine Ifit3 plays an essential role in restricting the replication and reducing the pathogenicity of RABV. Ifit3 acts synergistically with Ifit2 to inhibit RABV replication, providing further insight into the function and complexity of the Ifit family.

中文翻译：

---

鼠类 Ifit3 限制狂犬病病毒在体外和体内的复制

狂犬病病毒 (RABV) 感染可启动宿主免疫防御反应并诱导以干扰素 (IFN) 刺激基因 (ISG) 表达为特征的抗病毒状态，其中具有四肽重复序列的 IFN 诱导蛋白基因家族 (Ifits )是杰出的代表。在此，我们证明了在 RABV 感染后培养的细胞和小鼠大脑中 Ifit1、Ifit2 和 Ifit3 的 mRNA 和蛋白质水平高度增加。表达 Ifit3 的重组 RABV，命名为 rRABV-Ifit3，在肌肉注射后在 C57BL/6 小鼠中显示出比亲本 RABV 更低的致病性，并且 Ifit3 缺陷小鼠表现出对 RABV 感染的更高易感性和更高的 RABV 感染期间死亡率。而且，与他们各自的表情相比，体外。这些结果表明，鼠Ifit3在限制RABV复制和降低致病性方面发挥着重要作用。Ifit3 与 Ifit2 协同作用以抑制 RABV 复制，从而进一步了解 Ifit 家族的功能和复杂性。