文献类型： 外文期刊

作者： Wu, Xiangju ¹ ; Hu, Yue ¹ ; Sui, Chao ¹ ; Pan, Li ³ ; Yoo, Dongwan ⁴ ; Miller, Laura C. ⁵ ; Lee, Changhee ⁶ ; Cong, Xiaoyan ¹ ; Li, Juntong ¹ ; Du, Yijun ¹ ; Qi, Jing ¹ ;

作者机构： 1.Shandong Acad Agr Sci, Inst Anim Sci & Vet Med, Shandong Key Lab Anim Dis Control & Breeding, Jinan, Shandong, Peoples R China

2.Key Lab Livestock & Poultry Multiom MARA, Jinan, Shandong, Peoples R China

3.Chinese Acad Agr Sci, Lanzhou Vet Res Inst, State Key Lab Vet Etiol Biol,Minist Agr, Natl Foot & Mouth Dis Reference Lab,Key Lab Anim, Lanzhou, Gansu, Peoples R China

4.Univ Illinois, Dept Pathobiol, Urbana, IL USA

5.ARS, Virus & Prion Res Unit, Natl Anim Dis Ctr, USDA, Ames, IA USA

6.Gyeongsang Natl Univ, Coll Vet Med, Jinju, South Korea

7.Gyeongsang Natl Univ, Virus Vaccine Res Ctr, Jinju, South Korea

关键词： 3C protease; foot-and-mouth disease virus (FMDV); SUMOylation; replication

期刊名称：JOURNAL OF VIROLOGY （ 影响因子：6.549； 五年影响因子：5.78 ）

ISSN： 0022-538X

年卷期： 2022 年 96 卷 17 期

页码：

收录情况： SCI

摘要： Protein SUMOylation represents an important cellular process that regulates the activities of numerous host proteins as well as of many invasive viral proteins. Foot-and-mouth disease virus (FMDV) is the first animal virus discovered. However, whether SUMOylation takes place during FMDV infection and what role it plays in FMDV pathogenesis have not been investigated. In the present study, we demonstrated that SUMOylation suppressed FMDV replication by small interfering RNA (siRNA) transfection coupled with pharmaceutical inhibition of SUMOylation, which was further confirmed by increased virus replication for SUMOylation-deficient FMDV with mutations in 3C protease, a target of SUMOylation. Moreover, we provided evidence that four lysine residues, Lys-51, -54, -110, and -159, worked together to confer the SUMOylation to the FMDV 3C protease, which may make SUMOylation of FMDV 3C more stable and improve the host's chance of suppressing the replication of FMDV. This is the first report that four lysine residues can be alternatively modified by SUMOylation. Finally, we showed that SUMOylation attenuated the cleavage ability, the inhibitory effect of the interferon signaling pathway, and the protein stability of FMDV 3C, which appeared to correlate with a decrease in FMDV replication. Taken together, the results of our experiments describe a novel cellular regulatory event that significantly restricts FMDV replication through the SUMOylation of 3C protease. IMPORTANCE FMD is a highly contagious and economically important disease in cloven-hoofed animals. SUMOylation, the covalent linkage of a small ubiquitin-like protein to a variety of substrate proteins, has emerged as an important posttranslational modification that plays multiple roles in diverse biological processes. In this study, four lysine residues of FMDV 3C were found to be alternatively modified by SUMOylation. In addition, we demonstrated that SUMOylation attenuated FMDV 3C function through multiple mechanisms, including cleavage ability, the inhibitory effect of the interferon signaling pathway, and protein stability, which, in turn, resulted in a decrease of FMDV replication. Our findings indicate that SUMOylation of FMDV 3C serves as a host cell defense against FMDV replication. Further understanding of the cellular and molecular mechanisms driving this process should offer novel insights to design an effective strategy to control the dissemination of FMDV in animals. FMD is a highly contagious and economically important disease in cloven-hoofed animals. SUMOylation, the covalent linkage of a small ubiquitin-like protein to a variety of substrate proteins, has emerged as an important posttranslational modification that plays multiple roles in diverse biological processes.