Murine Ifit3 restricts the replication of Rabies virus both in vitro and in vivo
Murine Ifit3 restricts the replication of Rabies virus both in vitro and in vivo
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DOI：
10.1099/jgv.0.001619
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发表时间：
2021-01-01
影响因子：
3.8
通讯作者：
Zhao, Ling
中科院分区：
文献类型：
--
作者：
Chai, Benjie;Tian, Dayong;Zhao, Ling
狂犬病病毒（Rabies virus，RABV）感染可启动宿主的免疫防御反应，诱导以干扰素（IFN）刺激基因（interferon，ISGs）表达为特征的抗病毒状态，其中具有三肽重复序列的干扰素诱导蛋白（IFN-induced protein with tetratricopeptide repeats，Ifits）基因家族是突出的代表。在此，我们证明了Ifit 1，Ifit 2和Ifit 3的mRNA和蛋白水平在培养的细胞和小鼠脑RABV感染后高度增加。重组表达Ifit 3的RABV（rRABV-Ifit 3）对C57 BL/6小鼠的致病性低于亲本RABV，而Ifit 3缺陷型小鼠对RABV感染的易感性和死亡率较高。与单独表达相比，Ifit 2和Ifit 3共表达能更有效地抑制RABV的体外复制。这些结果表明，小鼠Ifit 3在限制复制和降低RABV的致病性中起重要作用。Ifit 3与Ifit 2协同作用以抑制RABV复制，从而提供对Ifit家族的功能和复杂性的进一步了解。
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.