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

Abstract

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

CLC Number:

R511.7

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.

Figures/Tables 4

Table 1

Fig. 1

Fig. 2

Fig. 3

References 32

1	SHORT K R , KROEZE E J B V , FOUCHIER R A M , et al. Pathogenesis of influenza-induced acute respiratory distress syndrome[J]. Lancet Infect Dis, 2014, 14 (1): 57- 69. doi: 10.1016/S1473-3099(13)70286-X
2	WASIK B R , VOORHEES I E H , PARRISH C R . Canine and feline influenza[J]. Cold Spring Harb Perspect Med, 2021, 11 (1): a038562. doi: 10.1101/cshperspect.a038562
3	SUN Y P , LIU J H . H9N2 influenza virus in China: a cause of concern[J]. Protein Cell, 2015, 6 (1): 18- 25. doi: 10.1007/s13238-014-0111-7
4	LEE D H , CRIADO M F , SWAYNE D E . Pathobiological origins and evolutionary history of highly pathogenic avian influenza viruses[J]. Cold Spring Harb Perspect Med, 2021, 11 (2): a038679. doi: 10.1101/cshperspect.a038679
5	ZHANG J H , HUANG L H , LIAO M , et al. H9N2 avian influenza viruses: challenges and the way forward[J]. Lancet Microbe, 2023, 4 (2): e70- e71. doi: 10.1016/S2666-5247(22)00305-6
6	SAGONG M , LEE K N , LEE E K , et al. Current situation and control strategies of H9N2 avian influenza in South Korea[J]. J Vet Sci, 2023, 24 (1): e5. doi: 10.4142/jvs.22216
7	BO-SHUN Z , LI L J , QIAN Z , et al. Co-infection of H9N2 influenza virus and Pseudomonas aeruginosa contributes to the development of hemorrhagic pneumonia in mink[J]. Vet Microbiol, 2020, 240, 108542. doi: 10.1016/j.vetmic.2019.108542
8	邢燕茹, 范春艳, 罗玉丽, 等. H9N2亚型禽流感病毒流行病学研究进展[J]. 中国家禽, 2021, 43 (10): 80- 86.
	XING Y R , FAN C Y , LUO Y L , et al. Advance on epidemiology of H9N2 subtype avian influenza virus[J]. China Poultry, 2021, 43 (10): 80- 86.
9	GU M , XU L J , WANG X Q , et al. Current situation of H9N2 subtype avian influenza in China[J]. Vet Res, 2017, 48 (1): 49. doi: 10.1186/s13567-017-0453-2
10	DHARMAYANTI N L P I , INDRIANI R , NURJANAH D . Vaccine efficacy on the novel reassortant H9N2 virus in indonesia[J]. Vaccines (Basel), 2020, 8 (3): 449. doi: 10.3390/vaccines8030449
11	JIANG Z M , WEI F H , ZHANG Y Y , et al. IFI16 directly senses viral RNA and enhances RIG-I transcription and activation to restrict influenza virus infection[J]. Nat Microbiol, 2021, 6 (7): 932- 945. doi: 10.1038/s41564-021-00907-x
12	OUYANG W , CEN M Y , YANG L P , et al. NMI facilitates influenza A virus infection by promoting degradation of IRF7 through TRIM21[J]. Am J Respir Cell Mol Biol, 2021, 65 (1): 30- 40. doi: 10.1165/rcmb.2020-0391OC
13	GÜNL F , KRISCHUNS T , SCHREIBER J A , et al. The ubiquitination landscape of the influenza A virus polymerase[J]. Nat Commun, 2023, 14 (1): 787. doi: 10.1038/s41467-023-36389-0
14	COCKRAM P E , KIST M , PRAKASH S , et al. Ubiquitination in the regulation of inflammatory cell death and cancer[J]. Cell Death Differ, 2021, 28 (2): 591- 605. doi: 10.1038/s41418-020-00708-5
15	吴玉湖, 胡欣妍, 杨宣叶, 等. 蛋白质泛素化修饰对流感病毒增殖和致病性的影响[J]. 病毒学报, 2023, 39 (4): 1152- 1160.
	WU Y H , HU X Y , YANG X Y , et al. Effects of ubiquitination on replication and pathogenesis of influenza virus[J]. Chinese Journal of Virology, 2023, 39 (4): 1152- 1160.
16	KAMEDA H , MIYOSHI H , SHIMIZU C , et al. Expression and regulation of neuromedin B in pituitary corticotrophs of male melanocortin 2 receptor-deficient mice[J]. Endocrinology, 2014, 155 (7): 2492- 2499. doi: 10.1210/en.2013-2077
17	YANG G H , HUANG H P , TANG M Y , et al. Role of neuromedin B and its receptor in the innate immune responses against influenza A virus infection in vitro and in vivo[J]. Vet Res, 2019, 50 (1): 80. doi: 10.1186/s13567-019-0695-2
18	KORDYUKOVA L V , SHTYKOVA E V , BARATOVA L A , et al. Matrix proteins of enveloped viruses: a case study of Influenza A virus M1 protein[J]. J Biomol Struct Dyn, 2019, 37 (3): 671- 690. doi: 10.1080/07391102.2018.1436089
19	DAHMANI I , LUDWIG K , CHIANTIA S . Influenza A matrix protein M1 induces lipid membrane deformation via protein multimerization[J]. Biosci Rep, 2019, 39 (8): BSR20191024. doi: 10.1042/BSR20191024
20	WANG S S , ZHAO Z D , BI Y H , et al. Tyrosine 132 phosphorylation of influenza A virus M1 protein is crucial for virus replication by controlling the nuclear import of M1[J]. J Virol, 2013, 87 (11): 6182- 6191. doi: 10.1128/JVI.03024-12
21	BARMAN S , ALI A , HUI E K W , et al. Transport of viral proteins to the apical membranes and interaction of matrix protein with glycoproteins in the assembly of influenza viruses[J]. Virus Res, 2001, 77 (1): 61- 69. doi: 10.1016/S0168-1702(01)00266-0
22	GÓMEZ-PUERTAS P , ALBO C , PÉREZ-PASTRANA E , et al. Influenza virus matrix protein is the major driving force in virus budding[J]. J Virol, 2000, 74 (24): 11538- 11547. doi: 10.1128/JVI.74.24.11538-11547.2000
23	NAYAK D P , BALOGUN R A , YAMADA H , et al. Influenza virus morphogenesis and budding[J]. Virus Res, 2009, 143 (2): 147- 161. doi: 10.1016/j.virusres.2009.05.010
24	BOULO S , AKARSU H , RUIGROK R W H , et al. Nuclear traffic of influenza virus proteins and ribonucleoprotein complexes[J]. Virus Res, 2007, 124 (1-2): 12- 21. doi: 10.1016/j.virusres.2006.09.013
25	BUI M , WILLS E G , HELENIUS A , et al. Role of the influenza virus M1 protein in nuclear export of viral ribonucleoproteins[J]. J Virol, 2000, 74 (4): 1781- 1786. doi: 10.1128/JVI.74.4.1781-1786.2000
26	YAMAUCHI Y . Influenza A virus uncoating[J]. Adv Virus Res, 2020, 106, 1- 38.
27	HOM N , GENTLES L , BLOOM J D , et al. Deep mutational scan of the highly conserved influenza A virus M1 matrix protein reveals substantial intrinsic mutational tolerance[J]. J Virol, 2019, 93 (13): e00161- 19.
28	唐梦瑶, 马逸杰, 田世茂, 等. 神经介素B及其受体NMBR参与抗A型流感病毒H1N1亚型感染的信号通路[J]. 畜牧兽医学报, 2021, 52 (11): 3215- 3223. doi: 10.11843/j.issn.0366-6964.2021.011.023
	TANG M Y , MA Y J , TIAN S M , et al. The signaling pathway of neuromedin B and its receptor NMBR involvement in anti-influenza A virus H1N1 subtype infection[J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52 (11): 3215- 3223. doi: 10.11843/j.issn.0366-6964.2021.011.023
29	MAHESUTIHAN M , ZHENG W N , CUI L , et al. CypA regulates AIP4-mediated M1 ubiquitination of influenza A virus[J]. Virol Sin, 2018, 33 (5): 440- 448. doi: 10.1007/s12250-018-0058-6
30	CERVIA L D , SHIBUE T , BORAH A A , et al. A ubiquitination cascade regulating the integrated stress response and survival in carcinomas[J]. Cancer Discov, 2023, 13 (3): 766- 795. doi: 10.1158/2159-8290.CD-22-1230
31	LI J Y , ZHU K , GU A H , et al. Feedback regulation of ubiquitination and phase separation of HECT E3 ligases[J]. Proc Natl Acad Sci U S A, 2023, 120 (33): e2302478120. doi: 10.1073/pnas.2302478120
32	KIRUI J , MONDAL A , MEHLE A . Ubiquitination upregulates influenza virus polymerase function[J]. J Virol, 2016, 90 (23): 10906- 10914. doi: 10.1128/JVI.01829-16

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

[1]	TIAN Shimao, WAN Qianhui, XU Xiaodong, KONG Yingying, TIAN Ke, TANG Yubing, CHEN Jilong, YANG Guihong. Ubiquitinase of NF-κB Signal Pathway Regulated by Neuromedin B and Its Receptor NMBR during Influenza A Virus H9N2 Subtype Infection [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(7): 3118-3126.
[2]	TANG Mengyao, MA Yijie, TIAN Shimao, WAN Qianhui, YANG Guihong. The Signaling Pathway of Neuromedin B and Its Receptor NMBR Involvement in Anti-influenza A Virus H1N1 Subtype Infection [J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(11): 3215-3223.
[3]	LI Jun, GAO Jingping, ZHANG Yaqi, LUO Qiang, LIANG Ting, LI Peiyao, WANG Shaohua, ZHANG Ruihua, XU Mingju, XU Tong. The Effect of TRPM2 Ion Channel on Mitochondrial Damage of Pulmonary Microvascular Endothelial Cells in Mice Infected with H9N2 Influenza Virus [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2019, 50(10): 2053-2060.
[4]	WANG Jian-lin, CAO Zhi-wei, WANG Dong-dong, YIN Yan-bo. Transcriptional Responses of TLR-7 and Mx mRNA in 3 Chicken Host Systems Infected with H9N2 Influenza Viruses with Different Pathogenicities [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2017, 48(5): 907-913.

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

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 4

References 32

Related Articles 4

Recommended Articles

Metrics

Comments