1. Murine Ifit3 restricts the replication of Rabies virus both in vitro and in vivo
- Author
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Bin Tian, Jie Pei, Dayong Tian, Yueming Yuan, Fei Huang, Ming Zhou, Yaping Yang, Benjie Chai, Qiong Wu, Ling Zhao, Lei Lv, Zhenfang Fu, Caiqian Wang, Wang Ke, and Baokun Sui
- Subjects
0301 basic medicine ,Messenger RNA ,Innate immune system ,030102 biochemistry & molecular biology ,Rabies virus ,Biology ,medicine.disease_cause ,Virology ,In vitro ,law.invention ,03 medical and health sciences ,Tetratricopeptide ,030104 developmental biology ,Interferon ,law ,medicine ,Recombinant DNA ,Gene ,medicine.drug - Abstract
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.
- Published
- 2021
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