非洲猪瘟病毒MGF360-14L靶向MAVS抑制Ⅰ型干扰素的产生

doi:10.11843/j.issn.0366-6964.2022.09.041

畜牧兽医学报 ›› 2022, Vol. 53 ›› Issue (9): 3272-3278.doi: 10.11843/j.issn.0366-6964.2022.09.041

• 研究简报 • 上一篇

非洲猪瘟病毒MGF360-14L靶向MAVS抑制Ⅰ型干扰素的产生

王洋¹, 崔帅¹, 鑫婷¹, 王西西², 于海男¹, 陈世钰¹, 蒋亚君¹, 高新桃³, 庞忠宝¹, 姜一曈¹, 郭晓宇¹, 贾红¹, 朱鸿飞^1*

1. 中国农业科学院北京畜牧兽医研究所, 北京 100193;
2. 中国科学院微生物研究所, 北京 100080;
3. 中国农业科学院生物技术研究所, 北京 100081

收稿日期:2022-01-10 出版日期:2022-09-23 发布日期:2022-09-23
通讯作者: 朱鸿飞,主要从事预防兽医学研究,E-mail:bioclub@vip.sina.com
作者简介:王洋(1990-),男,吉林公主岭人,博士生,主要从事预防兽医学研究,E-mail:wang691665@126.com
基金资助:
中国农业科学院基本科研业务费专项（Y2019YJ07-05）；国家重点研发计划（2021YFD1800008）

ASFV MGF360-14L Interacts with MAVS and Inhibit the Expression of Type Ⅰ Interferon

WANG Yang¹, CUI Shuai¹, XIN Ting¹, WANG Xixi², YU Hainan¹, CHEN Shiyu¹, JIANG Yajun¹, GAO Xintao³, PANG Zhongbao¹, JIANG Yitong¹, GUO Xiaoyu¹, JIA Hong¹, ZHU Hongfei^1*

1. Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China;
2. Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080, China;
3. Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China

Received:2022-01-10 Online:2022-09-23 Published:2022-09-23

摘要/Abstract

摘要： 本研究旨在探究非洲猪瘟病毒（African swine fever virus，ASFV）多基因家族成员MGF360-14L对Ⅰ型干扰素（IFN）的抑制作用及其作用机制。通过双荧光素酶试验检测MGF360-14L对线粒体抗病毒信号蛋白（MAVS）诱导的干扰素β（IFN-β）启动子活性的影响，免疫共沉淀和激光共聚焦检测MGF360-14L与MAVS的互作关系，及Western blot分析MGF360-14L对MAVS和TRIM21诱导的TBK1和IRF3磷酸化的影响。结果表明，ASFV非结构蛋白MGF360-14L抑制MAVS诱导的IFN-β启动子活性。MGF360-14L能够与MAVS互作，并且对MAVS和TRIM21诱导的TBK1和IRF3磷酸化具有抑制作用。此外，当过表达MGF360-14L时，MGF360-14L蛋白与TRIM21竞争结合MAVS，抑制TRIM21对MAVS的泛素化作用，从而降低IFN-β的水平。综上所述，MGF360-14L可能通过竞争性结合MAVS，抑制TRIM21对MAVS的泛素化，从而下调Ⅰ型IFN的产生。研究结果为探究ASFV的免疫逃逸机制提供了新线索。

关键词: 非洲猪瘟病毒, Ⅰ型干扰素, 线粒体抗病毒信号蛋白, 泛素化, 免疫逃逸

Abstract: This study was conducted to investigate the inhibitory effect of the African swine fever virus (ASFV) MGF360-14L on type Ⅰ interferon (IFN) and its mechanism. The effects of MGF360-14L on MAVS-induced IFN-β promoter activity were detected by dual luciferase assay, and the interaction between MGF360-14L and MAVS was examined by co-immunoprecipitation and indirect immunofluorescence assays. The results showed that the viral non-structural protein MGF360-14L inhibited interferon β (IFN-β) promoter activity induced by MAVS signaling. MGF360-14L interacted with MAVS and inhibited the phosphorylation of TBK1 and IRF3 induced by MAVS and TRIM21. In addition, MGFF360-14L competed with TRIM21 to bind MAVS and inhibit the TRIM21-mediated ubiquitination of MAVS, thereby reducing IFN-β levels. In conclusion, MGF360-14L may inhibit TRIM21-mediated ubiquitination of MAVS by competitively binding MAVS, thus down-regulating the production of type Ⅰ interferon. These findings provide new insights into the mechanisms underlying ASFV immune evasion.

Key words: African swine fever virus, type Ⅰ interferon, MAVS, ubiquitination, immune evasion

中图分类号:

S852.659.1

王洋, 崔帅, 鑫婷, 王西西, 于海男, 陈世钰, 蒋亚君, 高新桃, 庞忠宝, 姜一曈, 郭晓宇, 贾红, 朱鸿飞. 非洲猪瘟病毒MGF360-14L靶向MAVS抑制Ⅰ型干扰素的产生[J]. 畜牧兽医学报, 2022, 53(9): 3272-3278.

WANG Yang, CUI Shuai, XIN Ting, WANG Xixi, YU Hainan, CHEN Shiyu, JIANG Yajun, GAO Xintao, PANG Zhongbao, JIANG Yitong, GUO Xiaoyu, JIA Hong, ZHU Hongfei. ASFV MGF360-14L Interacts with MAVS and Inhibit the Expression of Type Ⅰ Interferon[J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(9): 3272-3278.

参考文献 21

[1]	DIXON L K, SUN H, ROBERTS H. African swine fever[J]. Antiviral Res, 2019, 165:34-41.
[2]	ALONSO C, BORCA M, DIXON L, et al. ICTV virus taxonomy profile:Asfarviridae[J]. J Gen Virol, 2018, 99(5):613-614.
[3]	SUN E C, HUANG L Y, ZHANG X F, et al. Genotype I African swine fever viruses emerged in domestic pigs in China and caused chronic infection[J]. Emerg Microbes Infect, 2021, 10(1):2183-2193.
[4]	LI D, YANG W P, LI L L, et al. African swine fever virus MGF-505-7R negatively regulates cGAS-STING-mediated signaling pathway[J]. J Immunol, 2021, 206(8):1844-1857.
[5]	LIU X L, AO D, JIANG S, et al. African swine fever virus A528R inhibits TLR8 mediated NF-κB activity by targeting p65 activation and nuclear translocation[J]. Viruses, 2021, 13(10):2046.
[6]	LI J N, SONG J, KANG L, et al. pMGF505-7R determines pathogenicity of African swine fever virus infection by inhibiting IL-1β and type I IFN production[J]. PLoS Pathog, 2021, 17(7):e1009733.
[7]	LI D, ZHANG J, YANG W P, et al. African swine fever virus protein MGF-505-7R promotes virulence and pathogenesis by inhibiting JAK1-and JAK2-mediated signaling[J]. J Biol Chem, 2021, 297(5):101190.
[8]	YANG K D, HUANG Q T, WANG R Y, et al. African swine fever virus MGF505-11R inhibits type I interferon production by negatively regulating the cGAS-STING-mediated signaling pathway[J]. Vet Microbiol, 2021, 263:109265.
[9]	LIU H S, ZHU Z X, FENG T, et al. African swine fever virus E120R protein inhibits interferon beta production by interacting with IRF3 to block its activation[J]. J Virol, 2021, 95(18):e00824-21.
[10]	SETH R B, SUN L J, EA C K, et al. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-κB and IRF3[J]. Cell, 2005, 122(5):669-682.
[11]	ZHOU D Y, LI Q Y, JIA F, et al. The Japanese encephalitis virus NS1' protein inhibits type I IFN production by targeting MAVS[J]. J Immunol, 2020, 204(5):1287-1298.
[12]	EKANAYAKA P, LEE S Y, HERATH T U B, et al. Foot-and-mouth disease virus VP1 target the MAVS to inhibit type-I interferon signaling and VP1 E83K mutation results in virus attenuation[J]. PLoS Pathog, 2020, 16(11):e1009057.
[13]	HE Z J, ZHU X, WEN W T, et al. Dengue virus subverts host innate immunity by targeting adaptor protein MAVS[J]. J Virol, 2016, 90(16):7219-7230.
[14]	XUE B B, LI H Y, GUO M M, et al. TRIM21 promotes innate immune response to RNA viral infection through Lys27-linked polyubiquitination of MAVS[J]. J Virol, 2018, 92(14):e00321-18.
[15]	WANG Y, CUI S, XIN T, et al. African swine fever virus MGF360-14L negatively regulates type I interferon signaling by targeting IRF3[J]. Front Cell Infect Microbiol, 2022, 11:818969.
[16]	O'DONNELL V, HOLINKA L G, GLADUE D P, et al. African swine fever virus Georgia isolate harboring deletions of MGF360 and MGF505 genes is attenuated in swine and confers protection against challenge with virulent parental virus[J]. J Virol, 2015, 89(11):6048-6056.
[17]	CHEN W Y, ZHAO D M, HE X J, et al. A seven-gene-deleted African swine fever virus is safe and effective as a live attenuated vaccine in pigs[J]. Sci China Life Sci, 2020, 63(5):623-634.
[18]	BORCA M V, O'DONNELL V, HOLINKA L G, et al. Development of a fluorescent ASFV strain that retains the ability to cause disease in swine[J]. Sci Rep, 2017, 7(1):46747.
[19]	YU K, TIAN H B, DENG H Y. PPM1G restricts innate immune signaling mediated by STING and MAVS and is hijacked by KSHV for immune evasion[J]. Sci Adv, 2020, 6(47):eabd0276.
[20]	XING J J, WANG S, LIN R T, et al. Herpes simplex virus 1 tegument protein US11 downmodulates the RLR signaling pathway via direct interaction with RIG-I and MDA-5[J]. J Virol, 2012, 86(7):3528-3540.
[21]	JIANG X F, TANG T, GUO J F, et al. Human herpesvirus 6B U26 inhibits the activation of the RLR/MAVS signaling pathway[J]. mBio, 2021, 12(1):e03505-20.

非洲猪瘟病毒MGF360-14L靶向MAVS抑制Ⅰ型干扰素的产生

ASFV MGF360-14L Interacts with MAVS and Inhibit the Expression of Type Ⅰ Interferon

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