The Influence of Newcastle Disease Virus Major Proteins on Virulence

Guozhong Zhang (The College of Veterinary Medicine,China Agricultural University)
Jia Xue (Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People’s Republic of China)
Xiao Li (Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People’s Republic of China)

Article ID: 4098


The Newcastle disease virus (NDV) negative-strand RNA genome containssix genes. These genes encode nucleoprotein (NP), phosphoprotein (P),matrix protein (M), fusion protein (F), hemagglutinin-neuraminidase (HN),and RNA-dependent RNA polymerase (L) proteins. The six proteins affectthe virulence of NDV in different ways, but available information on thesix proteins is disparate and scattered across many databases and sources.A comprehensive overview of the proteins determining NDV virulence islacking. This review summarizes the virulence of NDV as a complex traitdetermined by these six different proteins.


Newcastle disease virus , Structural protein ,Virulence

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[1] Fan W, Wang Y, Wang SH, et al. Virulence in Newcastle disease virus: A genotyping and molecular evolution spectrum perspective. Res Vet Sci. 2017, 111: 49-54.

[2] Dimitrov KM, Abolnik C, Afonso CL, et al. Updated unified phylogenetic classification system and revised nomenclature for Newcastle disease virus. Infect Genet Evol. 2019, 74: 103917.

[3] Diel DG, da Silva LHA, Liu HLet al. Genetic diversity of avian paramyxovirus type 1: proposal for a unified nomenclature and classification system of Newcastle disease virus genotypes. Infect Genet Evol. 2012, 12: 1770-1779.

[4] Yang HM, Zhao J, Xue J, et al. Antigenic variation of LaSota and genotype VII Newcastle disease virus (NDV) and their efficacy against challenge with velogenic NDV. Vaccine 2017, 35: 27-32.

[5] Rangaswamy US, Wang WJ, Cheng X, et al. Newcastle disease virus establishes persistent infection in tumor cells in vitro: contribution of the cleavage site of fusion protein and second sialic acid binding site of hemagglutinin-neuraminidase. J Virol. 2017, 91: e00770-17.

[6] Kaunas R, Huang Z, Hahn J. A kinematic model coupling stress fiber dynamics with JNK activation in response to matrix stretching. J Theor Biol. 2010, 264: 593-603.

[7] Yu X, Cheng JL, He ZR, et al. The glutamic residue at position 402 in the C-terminus of Newcastle disease virus nucleoprotein is critical for the virus. Sci Rep. 2017, 7: 17471.

[8] Alexander DJ. Newcastle disease and other avian paramyxoviruses. Rev Sci Tech. 2000, 19: 443-462.

[9] Cheng JH, Sun YJ, Zhang FQ, et al. Newcastle disease virus NP and P proteins induce autophagy via the endoplasmic reticulum stress-related unfolded protein response. Sci Rep. 2016, 6: 24721.

[10] Zhan Y, Yu SQ, Yang S, et al. Newcastle Disease virus infection activates PI3K/Akt/mTOR and p38 MAPK/Mnk1 pathways to benefit viral mRNA translation via interaction of the viral NP protein and host eIF4E. PLoS Pathog. 2020, 16: e1008610.

[11] Kumar R, Tiwari AK, Chaturvedi U, et al. Cloning and expression analysis of multiple proteins encoding P gene of Newcastle disease virus. Indian J Exp Biol. 2013, 51: 116-123.

[12] Pickar A, Xu P, Elson A, et al. Roles of serine and threonine residues of mumps virus P protein in viral transcription and replication. J Virol. 2014, 88: 4414-4422.

[13] Qiu, X., Fu Q, Meng C, et al. Kinetic analysis of RNA editing of Newcastle disease virus P gene in the early period of infection. Acta Virol. 2016, 60: 71-77.

[14] Park MS, Shaw ML, Muñoz-Jordan J, et al. Newcastle disease virus (NDV)-based assay demonstrates interferon-antagonist activity for the NDV V protein and the Nipah virus V, W, and C proteins. J Virol. 2003, 77: 1501-1511.

[15] Jang J, Hong SH, Choi D, et al. Overexpression of Newcastle disease virus (NDV) V protein enhances NDV production kinetics in chicken embryo fibroblasts. Appl Microbiol Biotechnol. 2010, 85: 1509-1520.

[16] Qiu X, Fu Q, Meng CC, et al. Newcastle disease virus V protein targets phosphorylated STAT1 to block IFN-I signaling. PLoS One. 2016, 11: e0148560.

[17] Wang, X., Jia YQ, Ren J, et al., Newcastle disease virus nonstructural V protein upregulates SOCS3 expression to facilitate viral replication depending on the MEK/ERK pathway. Front Cell Infect Microbiol. 2019, 9:317.

[18] Sun, Y., Zheng H, Yu SQ, et al. Newcastle disease virus V protein degrades mitochondrial antiviral signaling protein to inhibit host type I interferon production via E3 ubiquitin ligase RNF5. J Virol. 2019, 93: e00322-19.

[19] Karsunke J, Heiden S, Murr M, et al. W protein expression by Newcastle disease virus. Virus Res. 2019, 263: 207-216.

[20] Yang Y, Bu YW, Zhao J, et al. Appropriate amount of W protein of avian avulavirus 1 benefits viral replication and W shows strain-dependent subcellular localization. Virology. 2019, 538: 71-85.

[21] Yang Y, Xue J, Teng QY, et al. Mechanisms and consequences of Newcastle disease virus W protein subcellular localization in the nucleus or mitochondria. J Virol. 2021, 95: e02087-20.

[22] Harrison MS, Sakaguchi T, Schmitt AP. Paramyxovirus assembly and budding: building particles that transmit infections. Int J Biochem Cell Biol. 2010, 42: 1416–1429.

[23] Rajani KR, Kneller ELP, McKenzie MO, et al. Complexes of vesicular stomatitis virus matrix protein with host Rae1 and Nup98 involved in inhibition of host transcription. PLoS Pathog. 2012, 8: e1002929.

[24] Peeples ME, Wang C, Gupta KC, et al. Nuclear entry and nucleolar localization of the Newcastle disease virus (NDV) matrix protein occur early in infection and do not require other NDV proteins. J Virol. 1992, 66: 3263-9.

[25] Duan Z, Li J, Zhu J, et al. A single amino acid mutation, R42A, in the Newcastle disease virus matrix protein abrogates its nuclear localization and attenuates viral replication and pathogenicity. J Gen Virol. 2014, 95: 1067-1073.

[26] Li X, Li XQ, Cao H, et al. Engagement of new castle disease virus (NDV) matrix (M) protein with charged multivesicular body protein (CHMP) 4 facilitates viral replication. Virus Res. 2013, 171: 80-88.

[27] Duan Z, Chen J, He L, et al. [Matrix protein of Newcastle disease virus interacts with avian nucleophosmin B23. 1 in HEK-293T cells]. Wei Sheng Wu Xue Bao. 2013, 53: 730-736.

[28] Duan Z, Hu ZL, Zhu J, et al. Mutations in the FPIV motif of Newcastle disease virus matrix protein attenuate virus replication and reduce virus budding. Arch Virol. 2014, 159: 1813-1819.

[29] Sun C, Wen HL, Chen YZ, et al. Roles of the highly conserved amino acids in the globular head and stalk region of the Newcastle disease virus HN protein in the membrane fusion process. Biosci Trends. 2015, 9: 56-64.

[30] Vialard J, Lalumière M, Vernet T, et al. Synthesis of the membrane fusion and hemagglutinin proteins of measles virus, using a novel baculovirus vector containing the beta-galactosidase gene. J Virol. 1990, 64: 37-50.

[31] McGinnes Cullen L, Schmidt MR, Kenward SA, et al. Murine immune responses to virus-like particle-associated pre- and postfusion forms of the respiratory syncytial virus F protein. J Virol. 2015, 89: 6835-6847.

[32] Kim SH, Chen ZY, Yoshida A, et al. Evaluation of fusion protein cleavage site sequences of Newcastle disease virus in genotype matched vaccines. PLoS One. 2017, 12: e0173965.

[33] Hodder AN, Selleck PW, White JR, et al. Analysis of pathotype-specific structural features and cleavage activation of Newcastle disease virus membrane glycoproteins using antipeptide antibodies. J Gen Virol. 1993, 74: 1081-1091.

[34] Huang Y, Liu YQ, Li YG, et al. Role of key amino acids in the transmembrane domain of the Newcastle disease virus fusion protein. Biosci Trends. 2021, 15: 16-23.

[35] Rajmani RS, Gandham RK, Gupta SK, et al. HN protein of Newcastle disease virus induces apoptosis through SAPK/JNK pathway. Appl Biochem Biotechnol. 2015, 177: 940-956.

[36] Mirza AM, Iorio RM. A mutation in the stalk of the newcastle disease virus hemagglutinin-neuraminidase (HN) protein prevents triggering of the F protein despite allowing efficient HN-F complex formation. J Virol. 2013, 87: 8813-8815.

[37] Liu B, Ji YH, Lin ZQ, et al. Two single amino acid substitutions in the intervening region of Newcastle disease virus HN protein attenuate viral replication and pathogenicity. Sci Rep. 2015, 5: 13038.

[38] Mahon PJ, Mirza AM, Iorio RM. Role of the two sialic acid binding sites on the newcastle disease virus HN protein in triggering the interaction with the F protein required for the promotion of fusion. J Virol. 2011, 85: 12079-12082.

[39] Sato H, Hattori S, Ishidaet N, et al. Nucleotide sequence of the hemagglutinin-neuraminidase gene of Newcastle disease virus avirulent strain D26: evidence for a longer coding region with a carboxyl terminal extension as compared to virulent strains. Virus Res. 1987, 8: 217-232.

[40] Jin J, Zhao J, Ren YC, et al. Contribution of HN protein length diversity to Newcastle disease virus virulence, replication and biological activities. Sci Rep. 2016, 6: 36890.

[41] Ke GM, Chuang KP, Chang CD, et al. Analysis of sequence and haemagglutinin activity of the HN glycoprotein of Newcastle disease virus. Avian Pathol. 2010, 39: 235-244.

[42] Zhao W, Zhang ZY, Zsak L, et al. Effects of the HN gene C-terminal extensions on the Newcastle disease virus virulence. Virus Genes. 2013, 47: 498-504.

[43] Jin JH, Cheng JL, He ZR, et al. Different origins of Newcastle disease virus hemagglutinin-neuraminidase protein modulate the replication efficiency and pathogenicity of the virus. Front Microbiol. 2017, 8: 1607.

[44] Rout SN, Samal SK. The large polymerase protein is associated with the virulence of Newcastle disease virus. J Virol. 2008, 82: 7828-7836.

[45] Yu XH, Cheng JL, Xue J, et al. Roles of the polymerase-associated protein genes in Newcastle disease virus virulence. Front Microbiol. 2017, 8: 161.

[46] Ganar K, Das M, Sinha S, et al. Newcastle disease virus: current status and our understanding. Virus Res. 2014, 184: 71-81.

[47] Dortmans JC, Koch G, Rottier PJ, et al. Virulence of Newcastle disease virus: what is known so far? Vet Res. 2011, 42: 122.



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