神经介素B和受体对H9N2亚型流感病毒感染诱导的ITCH表达的影响

doi:10.11843/j.issn.0366-6964.2025.04.031

畜牧兽医学报 ›› 2025, Vol. 56 ›› Issue (4): 1834-1842.doi: 10.11843/j.issn.0366-6964.2025.04.031

神经介素B和受体对H9N2亚型流感病毒感染诱导的ITCH表达的影响

田世茂, 田珂, 刘玉钤, 辜晴新, 沈昀知, 张骋怀, 包银莉, 杨桂红*()

福建农林大学动物科学学院闽台动物病原生物学重点实验室, 福州 350002

收稿日期:2024-05-27 出版日期:2025-04-23 发布日期:2025-04-28
通讯作者: 杨桂红 E-mail:yangguihong@fafu.edu.cn
作者简介:田世茂(1998-), 女, 贵州贵阳人, 硕士研究生, 主要从事小肽在动物病毒性疾病中的免疫调节作用研究
田珂(2001-), 女, 河南周口人, 硕士研究生, 主要从事小肽在动物病毒性疾病中的免疫调节作用研究
第一联系人：
田世茂和田珂为同等贡献作者
基金资助:
国家自然科学基金重点项目(U23A20235)；国家自然科学基金项目(32030110)；福建农林大学科技创新项目(KFB23100；KFB23094)；福建农林大学大学生创业实践项目(202410389447)；动物源性人兽共患病防控福建省高校工程研究中心开放基金课题项目(2023K05)

Effect of Neuromedin B and Receptors on ITCH Expression Induced by H9N2 Subtype Influenza Virus Infection

TIAN Shimao, TIAN Ke, LIU Yuqian, GU Qingxin, SHEN Yunzhi, ZHANG Chenghuai, BAO Yinli, YANG Guihong*()

Key Laboratory of Fujian-Taiwan Animal pathogen Biology, College of Animal Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China

Received:2024-05-27 Online:2025-04-23 Published:2025-04-28
Contact: YANG Guihong E-mail:yangguihong@fafu.edu.cn

摘要/Abstract

摘要：

甲型流感病毒(IAV)编码的基质蛋白1(M1)通过调控E3泛素连接酶ITCH介导的泛素化修饰反应拮抗宿主的抗病毒免疫反应。本课题前期研究表明，神经介素B(NMB)和其受体NMBR具有抑制IAV的先天性免疫应答反应的作用，但二者对IAV感染诱导的E3泛素连接酶ITCH和M1表达的影响如何，尚未见报道。因此，本文采用外源性NMB及H9N2亚型禽流感病毒刺激模型，适时干扰和过表达NMBR，分别从体内外水平分析NMB和NMBR对ITCH和M1蛋白的表达水平的影响。结果显示：添加外源性NMB和过表达NMBR均可显著抑制H9N2亚型禽流感病毒感染的A549细胞和小鼠肺组织中ITCH表达；与之相对，干扰NMBR表达则可显著促进A549细胞和小鼠肺组织中ITCH表达；此外，NMB和NMBR对H9N2亚型禽流感病毒感染诱导的ITCH的表达趋势与M1蛋白的表达呈现正相关。以上结果表明，NMB和NMBR可通过调节ITCH的表达而影响H9N2编码的M1蛋白的表达，从而发挥抗H9N2亚型禽流感病毒感染的先天性免疫反应。

关键词: 神经介素B, 神经介素B受体NMBR, H9N2流感病毒, E3泛素连接酶ITCH

Abstract:

Matrix protein 1 (M1), encoded by influenza A virus (IAV) ubiquitin ligase, antagonizes the host's antiviral immune response by modulating the E3 ITCH-mediated ubiquitination. The previous studies in this study showed that neurointerleukin B (NMB) and its receptor NMBR could inhibit the innate immune response of IAV, however, their effects on the expression of ubiquitin ligase ITCH induced by IAV infection have not been reported. In this study, the effects of NMB and NMBR on the expression of ITCH and M1 protein were analyzed in vitro and in vivo by using an avian influenza virus stimulation model of NMB H9N2 subtype. The results showed that exogenous NMB and overexpression of NMBR could significantly inhibit ITCH expression in H9N2 avian influenza infected A549 cells and lung tissues of mice, interference of NMBR expression could significantly promote ITCH expression in A549 cells and lung tissue of mice, the expression trend of NMB and NMBR in ITCH induced by H9N2 avian influenza virus infection was positively correlated with the expression of M1 protein. These results suggest that NMB and NMBR can affect the expression of M1 protein encoded by H9N2 by regulating the expression of ITCH, thus exerting the innate immune response against H9N2 avian influenza virus infection.

Key words: neuromedin B, neuromedin B receptor NMBR, H9N2 influenza virus, E3 ubiquitin ligase ITCH

中图分类号:

R511.7

田世茂, 田珂, 刘玉钤, 辜晴新, 沈昀知, 张骋怀, 包银莉, 杨桂红. 神经介素B和受体对H9N2亚型流感病毒感染诱导的ITCH表达的影响[J]. 畜牧兽医学报, 2025, 56(4): 1834-1842.

TIAN Shimao, TIAN Ke, LIU Yuqian, GU Qingxin, SHEN Yunzhi, ZHANG Chenghuai, BAO Yinli, YANG Guihong. Effect of Neuromedin B and Receptors on ITCH Expression Induced by H9N2 Subtype Influenza Virus Infection[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(4): 1834-1842.

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引物名称 Names of primers	引物序列(5′→3′) Sequences of primers
IAV/H9N2 M1 Forward IAV/H9N2 M1 Reverse Human NMBR Forward Human NMBR Reverse Human ITCH Forward Human ITCH Reverse Human GAPDH Forward Human GAPDH Reverse Mouse NMBR Forward Mouse NMBR Reverse Mouse ITCH Forward Mouse ITCH Reverse Mouse β-actin Forward Mouse β-actin Reverse	CCATCAGGCCCCCTCAAAGCCGAGA ACGGTGAGCGTGAACACGAACCCTA TATTTCCTCATACCACTTGC CGTTTCCGTGTTTCCATCTGT ATTGCCATGGCTCTGTTCCA TTCTGTGGTCCATTGCTCCC AGAAGGCTGGGGCTCATTTG AGGGGCCATCCACAGTCTTC CATGCGGAATGTCCCTAACATC CCAAGCTACCAATGCGTGCTAC TGGGTAGTCTGACCATGAAATCT GGGGTAACAATAACTGTGAGG AATGGGTCAGAAGGACTCCT ACGGTTGGCCTTAGGGTTCAG

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神经介素B和受体对H9N2亚型流感病毒感染诱导的ITCH表达的影响

Effect of Neuromedin B and Receptors on ITCH Expression Induced by H9N2 Subtype Influenza Virus Infection

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