IFITM3 restricts RABV infection through inhibiting viral entry and mTORC1-dependent autophagy

Ma, Jiaqi1,2; Tu, Zhongzhong1; Du, Shouwen4; Zhang, Xinying1; Wang, Jie1,3; Guo, Jianxiong1; Feng, Ye1; He, Hongbin2; Wang, Hongmei2; Li, Chang1; Tu, Changchun1; Liu, Yan1

2023-09-01

10.1016/j.vetmic.2023.109823

VETERINARY MICROBIOLOGY   Impact Factor & Quartile

0378-1135

1873-2542

Rabies, which caused by rabies virus (RABV), is a zoonotic and life-threatening disease with 100% mortality, and there is no effective treatment thus far due to the unclear pathogenesis and less of treatment targets. Interferon-induced transmembrane protein 3 (IFITM3) has recently been identified as an important anti-viral host effector induced by type I interferon. However, the role of IFITM3 in RABV infection has not been elucidated. In this study, we demonstrated that IFITM3 is a crucial restriction factor for RABV, the viral-induced IFITM3 significantly inhibited RABV replication, while knockdown of IFITM3 had the opposite effect. We then identified that IFN beta induces the upregulation of IFITM3 in the absence or presence of RABV infection, meanwhile, IFITM3 positively regulates RABV-triggered production of IFN beta in a feedback manner. In-depth research we found that IFITM3 not only inhibits the virus absorb and entry, but also inhibits viral replication through mTORC1dependent autophagy. All these findings broaden our understanding of IFITM3 function and uncover a novel mechanism against RABV infection.

IFITM3 RABV IFN beta Autophagy Anti-viral effect

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English

Others

National Nat-ural Science Foundation of China["31972720","32273093","31902307","31972719"] ; National Key Research and Development Program of China[2022YFD1800100] ; Guangdong Provincial Science and Technology Plan Project[2021B121030015]

Microbiology ; Veterinary Sciences

Microbiology ; Veterinary Sciences

WOS:001031849300001

ELSEVIER

PLANT & ANIMAL SCIENCE

Web of Science

1.Chinese Acad Agr Sci, Changchun Vet Res Inst, Changchun 130122, Peoples R China
2.Shandong Normal Univ, Coll Life Sci, Ruminant Dis Res Ctr, Jinan 250014, Peoples R China
3.Northeast Normal Univ, Engn Res Ctr Glycoconjugates, Sch Life Sci, Minist Educ,Jinlin Prov Key Lab Chem & Biol Changb, Changchun 130024, Peoples R China
4.Southern Univ Sci & Technol, Jinan Univ, Shenzhen Peoples Hosp, Affiliated Hosp 1,Clin Med Coll 2,Dept Infect Dis, Shenzhen 518020, Guangdong, Peoples R China

Ma, Jiaqi,Tu, Zhongzhong,Du, Shouwen,et al. IFITM3 restricts RABV infection through inhibiting viral entry and mTORC1-dependent autophagy[J]. VETERINARY MICROBIOLOGY,2023,284.

Ma, Jiaqi.,Tu, Zhongzhong.,Du, Shouwen.,Zhang, Xinying.,Wang, Jie.,...&Liu, Yan.(2023).IFITM3 restricts RABV infection through inhibiting viral entry and mTORC1-dependent autophagy.VETERINARY MICROBIOLOGY,284.

Ma, Jiaqi,et al."IFITM3 restricts RABV infection through inhibiting viral entry and mTORC1-dependent autophagy".VETERINARY MICROBIOLOGY 284(2023).