牛冠状病毒刺突蛋白研究进展

doi:10.11843/j.issn.0366-6964.2024.03.009

摘要/Abstract

摘要： 牛冠状病毒（bovine coronavirus，BCoV）是一种能感染牛肠道、呼吸道引起新生犊牛腹泻、成年牛冬季痢疾和各年龄段的牛呼吸道疾病的重要病原体，严重危害着养牛业的发展。刺突（spike，S）蛋白是该病毒主要的结构蛋白和免疫原性蛋白，在病毒初始感染和诱导保护性免疫中发挥重要作用。本文就该病毒刺突蛋白的结构特征、生物学功能及应用研究、免疫原性、变异原因和潜在双受体系统的最新研究进展做一阐述，期望为新型疫苗研制和靶点治疗药物开发提供科学依据，以便制定快速有效的安全防治对策应对预出现的新毒株。

关键词: 牛冠状病毒, 刺突蛋白, 生物学功能, 蛋白变异

Abstract: Bovine coronavirus is an important pathogen that can infect bovine intestinal tract, respiratory tract and cause calf diarrhea, adult winter dysentery and bovine respiratory diseases of all ages, which seriously endangers the development of cattle industry. The spike protein is the main structural protein and immunogenic protein of the virus, which plays an important role in the initial infection of the virus and the induction of protective immunity. This paper describes the structural features, biological functions and application studies of the virulence of the spike protein, as well as its immunogenicity, causes of mutation and the latest research progress of the potential dual-receptor system, with the hope of providing a scientific basis for the development of a new type of vaccine and target therapeutic drugs, so as to formulate a rapid and effective safe prevention and control countermeasures to deal with the emergence of new strains of the disease.

Key words: bovine coronavirus, spike protein, biological function, protein variation

中图分类号:

S852.65

刘强, 牛小霞, 方敏, 刘艳玲, 高辉, 陈吉祥, 加华才让, 张思浓, 李勇. 牛冠状病毒刺突蛋白研究进展[J]. 畜牧兽医学报, 2024, 55(3): 944-956.

LIU Qiang, NIU Xiaoxia, FANG Min, LIU Yanling, GAO Hui, CHEN Jixiang, JIAHUA Cairang, ZHANG Sinong, LI Yong. Research Progress of Bovine Coronavirus Spike Protein[J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(3): 944-956.

参考文献

[1] MEBUS C A, STAIR E L, RHODES M B, et al.Pathology of neonatal calf diarrhea induced by a coronavirus-like agent[J].Vet Pathol, 1973, 10(1):45-64.
[2] KORBER B, FISCHER W M, GNANAKARAN S, et al.Tracking changes in SARS-CoV-2 Spike:evidence that D614G increases infectivity of the COVID-19 virus[J].Cell, 2020, 182(4):812-827.e19.
[3] LIU H L, ZHANG Q Q, WEI P C, et al.The basis of a more contagious 501Y.V1 variant of SARS-CoV-2[J].Cell Res, 2021, 31(6):720-722.
[4] CHEN A T, ALTSCHULER K, ZHAN S H, et al.COVID-19 CG enables SARS-CoV-2 mutation and lineage tracking by locations and dates of interest[J].Elife, 2021, 10:e63409.
[5] JEVŠNIK VIRANT M,ČERNE D, PETROVEC M, et al.Genetic characterisation and comparison of three human coronaviruses (HKU1, OC43, 229E) from patients and bovine coronavirus (BCoV) from cattle with respiratory disease in Slovenia[J].Viruses, 2021, 13(4):676.
[6] YESILBAG K, TOKER E B, ATES O.Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV, BPIV-3, BoHV-1, BCoV and BVDV) in vitro[J].Virus Res, 2021, 297:198384.
[7] GALAN L E B, SANTOS N M D, ASATO M S, et al.Phase 2 randomized study on chloroquine, hydroxychloroquine or ivermectin in hospitalized patients with severe manifestations of SARS-CoV-2 infection[J].Pathog Glob Health, 2021, 115(4):235-242.
[8] BIDOKHTI M R M, TRÅVÉN M, KRISHNA N K, et al.Evolutionary dynamics of bovine coronaviruses:natural selection pattern of the spike gene implies adaptive evolution of the strains[J].J Gen Virol, 2013, 94(Pt 9):2036-2049.
[9] SUZUKI K, HIROAKI H, KOHDA D, et al.An isoleucine zipper peptide forms a native-like triple stranded coiled coil in solution[J].Protein Eng, 1998, 11(11):1051-1055.
[10] SHAIK M M, PENG H Q, LU J M, et al.Structural basis of coreceptor recognition by HIV-1 envelope spike[J].Nature, 2019, 565(7739):318-323.
[11] FEHR A R, PERLMAN S.Coronaviruses:an overview of their replication and pathogenesis[M]//MAIER H, BICKERTON E, BRITTON P.Coronaviruses.New York:Humana Press, 2015:1-23.
[12] GALLAGHER T M, BUCHMEIER M J.Coronavirus spike proteins in viral entry and pathogenesis[J].Virology, 2001, 279(2):371-374.
[13] LIU L H, HAGGLUND S, HAKHVERDYAN M, et al.Molecular epidemiology of bovine coronavirus on the basis of comparative analyses of the S gene[J].J Clin Microbiol, 2006, 44(3):957-960.
[14] FOLLIS K E, YORK J, NUNBERG J H.Furin cleavage of the SARS coronavirus spike glycoprotein enhances cell-cell fusion but does not affect virion entry[J].Virology, 2006, 350(2):358-369.
[15] MENACHERY V D, DINNON III K H, YOUNT B L JR, et al.Trypsin treatment unlocks barrier for zoonotic bat coronavirus infection[J].J Virol, 2020, 94(5):e01774-19.
[16] SASAKI M, TOBA S, ITAKURA Y, et al.SARS-CoV-2 bearing a mutation at the S1/S2 cleavage site exhibits attenuated virulence and confers protective immunity[J].mBio, 2021, 12(4):e0141521.
[17] YUAN H W, WEN H L.Research progress on coronavirus S proteins and their receptors[J].Arch Virol, 2021, 166(7):1811-1817.
[18] VILČEK S, JACKOVÁ A, KOLESÁROVÁ M, et al.Genetic variability of the S1 subunit of enteric and respiratory bovine coronavirus isolates[J].Acta Virol, 2017, 61(2):212-216.
[19] KUBO H, YAMADA Y K, TAGUCHI F.Localization of neutralizing epitopes and the receptor-binding site within the amino-terminal 330 amino acids of the murine coronavirus spike protein[J].J Virol, 1994, 68(9):5403-5410.
[20] KREMPL C, SCHULTZE B, LAUDE H, et al.Point mutations in the S protein connect the sialic acid binding activity with the enteropathogenicity of transmissible gastroenteritis coronavirus[J].J Virol, 1997, 71(4):3285-3287.
[21] LANG Y F, LI W T, LI Z S, et al.Coronavirus hemagglutinin-esterase and spike proteins coevolve for functional balance and optimal virion avidity[J].Proc Natl Acad Sci U S A, 2020, 117(41):25759-25770.
[22] YOO D, DEREGT D.A single amino acid change within antigenic domain II of the spike protein of bovine coronavirus confers resistance to virus neutralization[J].Clin Diagn Lab Immunol, 2001, 8(2):297-302.
[23] SAIF L J.Bovine respiratory coronavirus[J].Vet Clin North Am Food Anim Pract, 2010, 26(2):349-364.
[24] HODNIK J J, JEŽEK J, STARIČJ.Coronaviruses in cattle[J].Trop Anim Health Prod, 2020, 52(6):2809-2816.
[25] JEONG J H, KIM G Y, YOON S S, et al.Molecular analysis of S gene of spike glycoprotein of winter dysentery bovine coronavirus circulated in Korea during 2002-2003[J].Virus Res, 2005, 108(1-2):207-212.
[26] ZHANG L Z, JACKSON C B, MOU H H, et al.SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity[J].Nat Commun, 2020, 11(1):6013.
[27] HASOKSUZ M, SREEVATSAN S, CHO K O, et al.Molecular analysis of the S1 subunit of the spike glycoprotein of respiratory and enteric bovine coronavirus isolates[J].Virus Res, 2002, 84(1-2):101-109.
[28] HAN M G, CHEON D S, ZHANG X M, et al.Cross-protection against a human enteric coronavirus and a virulent bovine enteric coronavirus in gnotobiotic calves[J].J Virol, 2006, 80(24):12350-12356.
[29] BOK M, MIÑO S, RODRIGUEZ D, et al.Molecular and antigenic characterization of bovine Coronavirus circulating in Argentinean cattle during 1994-2010[J].Vet Microbiol, 2015, 181(3-4):221-229.
[30] The Bovine Respiratory Disease Complex Coordinated Agricultural Project Research Team.Rapid Communication:Subclinical bovine respiratory disease-loci and pathogens associated with lung lesions in feedlot cattle[J].J Anim Sci, 2017, 95(6):2726-2731.
[31] KISER J N, NEIBERGS H L.Identifying loci associated with bovine corona virus infection and bovine respiratory disease in dairy and feedlot cattle[J].Front Vet Sci, 2021, 8:679074.
[32] SUZUKI T, OTAKE Y, UCHIMOTO S, et al.Genomic characterization and phylogenetic classification of bovine coronaviruses through whole genome sequence analysis[J].Viruses, 2020, 12(2):183.
[33] LI F.Evidence for a common evolutionary origin of coronavirus spike protein receptor-binding subunits[J].J Virol, 2012, 86(5):2856-2858.
[34] YANG S L, LI Y, DAI L P, et al.Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults:two randomised, double-blind, placebo-controlled, phase 1 and 2 trials[J].Lancet Infect Dis, 2021, 21(8):1107-1119.
[35] DEREGT D, GIFFORD G A, IJAZ M K, et al.Monoclonal antibodies to bovine coronavirus glycoproteins E2 and E3:demonstration of in vivo virus-neutralizing activity[J].J Gen Virol, 1989, 70(Pt 4):993-998.
[36] FRANZO G, DRIGO M, LEGNARDI M, et al.Bovine coronavirus:variability, evolution, and dispersal patterns of a No longer neglected betacoronavirus[J].Viruses, 2020, 12(11):1285.
[37] VAUTHEROT J F, MADELAINE M F, BOIREAU P, et al.Bovine coronavirus peplomer glycoproteins:detailed antigenic analyses of S1, S2 and HE[J].J Gen Virol, 1992, 73(Pt 7):1725-1737.
[38] PICCOLI L, PARK Y J, TORTORICI M A, et al.Mapping neutralizing and immunodominant sites on the SARS-CoV-2 spike receptor-binding domain by structure-guided high-resolution serology[J].Cell, 2020, 183(4):1024-1042.e21.
[39] WANG Z Z, POPOWSKI K D, ZHU D S, et al.Exosomes decorated with a recombinant SARS-CoV-2 receptor-binding domain as an inhalable COVID-19 vaccine[J].Nat Biomed Eng, 2022, 6(7):791-805.
[40] JIANG S B, BOTTAZZI M E, DU L Y, et al.Roadmap to developing a recombinant coronavirus S protein receptor-binding domain vaccine for severe acute respiratory syndrome[J].Expert Rev Vacc, 2012, 11(12):1405-1413.
[41] SUN Y S, ZHOU J J, ZHU H P, et al.Development of a recombinant RBD subunit vaccine for SARS-CoV-2[J].Viruses, 2021, 13(10):1936.
[42] ROGERS T F, ZHAO F Z, HUANG D L, et al.Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model[J].Science, 2020, 369(6506):956-963.
[43] GUO Y J, SUN S H, WANG K Y, et al.Elicitation of immunity in mice after immunization with the S2 subunit of the severe acute respiratory syndrome coronavirus[J].Dna Cell Biol, 2005, 24(8):510-515.
[44] ZHU Q H, SU M J, LI Z J, et al.Epidemiological survey and genetic diversity of bovine coronavirus in Northeast China[J].Virus Res, 2022, 308:198632.
[45] DAVID D, STORM N, ILAN W, et al.Characterization of winter dysentery bovine coronavirus isolated from cattle in Israel[J].Viruses, 2021, 13(6):1070.
[46] SEVINC TEMIZKAN S, ALKAN F.Bovine coronavirus infections in Turkey:molecular analysis of the full-length spike gene sequences of viruses from digestive and respiratory infections[J].Arch Virol, 2021, 166(9):2461-2468.
[47] MARTÍNEZ N, BRANDÃO P E, DE SOUZA S P, et al.Molecular and phylogenetic analysis of bovine coronavirus based on the spike glycoprotein gene[J].Infect Genet Evol, 2012, 12(8):1870-1878.
[48] KANNO T, HATAMA S, ISHIHARA R, et al.Molecular analysis of the S glycoprotein gene of bovine coronaviruses isolated in Japan from 1999 to 2006[J].J Gen Virol, 2007, 88(Pt 4):1218-1224.
[49] WANG Y Q, LIU D, SHI W F, et al.Origin and possible genetic recombination of the middle east respiratory syndrome coronavirus from the first imported case in China:phylogenetics and coalescence analysis[J].mBio, 2015, 6(5):e01280-15.
[50] SALEM E, DHANASEKARAN V, CASSARD H, et al.Global transmission, spatial segregation, and recombination determine the long-term evolution and epidemiology of bovine coronaviruses[J].Viruses, 2020, 12(5):534.
[51] DOMANSKA-BLICHARZ K, SAJEWICZ-KRUKOWSKA J.Recombinant turkey coronavirus:are some S gene structures of gammacoronaviruses especially prone to exchange?[J].Poult Sci, 2021, 100(4):101018.
[52] MINAMI S, KURODA Y, TERADA Y, et al.Detection of novel ferret coronaviruses and evidence of recombination among ferret coronaviruses[J].Virus Genes, 2016, 52(6):858-862.
[53] LU S, WANG Y Q, CHEN Y Z, et al.Discovery of a novel canine respiratory coronavirus support genetic recombination among betacoronavirus1[J].Virus Res, 2017, 237:7-13.
[54] ULRICH L, WERNIKE K, HOFFMANN D, et al.Experimental infection of cattle with SARS-CoV-2[J].Emerg Infect Dis, 2020, 26(12):2979-2981.
[55] ISLAM A, FERDOUS J, ISLAM S, et al.Evolutionary dynamics and epidemiology of endemic and emerging coronaviruses in humans, domestic animals, and wildlife[J].Viruses, 2021, 13(10):1908.
[56] FRANZO G, LEGNARDI M, TUCCIARONE C M, et al.Evolution of infectious bronchitis virus in the field after homologous vaccination introduction[J].Vet Res, 2019, 50(1):92.
[57] CAMPS M, HERMAN A, LOH E, et al.Genetic constraints on protein evolution[J].Crit Rev Biochem Mol Biol, 2007, 42(5):313-326.
[58] GENG H L, MENG X Z, YAN W L, et al.Prevalence of bovine coronavirus in cattle in China:A systematic review and meta-analysis[J].Microb Pathog, 2023, 176:106009.
[59] AMER H M.Bovine-like coronaviruses in domestic and wild ruminants[J].Anim Health Res Rev, 2018, 19(2):113-124.
[60] OLVERA-CHÁVEZ A, MEDINA-FIGUEROA A M.Clinical problem solving as a measurement instrument in a diploma course for respiratory technicians[J].Cir Cir, 2007, 75(4):271-274.
[61] SHANGJIN C, CORTEY M, SEGALÉS J.Phylogeny and evolution of the NS1 and VP1/VP2 gene sequences from porcine parvovirus[J].Virus Res, 2009, 140(1-2):209-215.
[62] ZHU Q H, LI B, SUN D B.Advances in bovine coronavirus epidemiology[J].Viruses, 2022, 14(5):1109.
[63] YANG Z H.The power of phylogenetic comparison in revealing protein function[J].Proc Natl Acad Sci U S A, 2005, 102(9):3179-3180.
[64] YOO D, PARKER M D, BABIUK L A.The S2 subunit of the spike glycoprotein of bovine coronavirus mediates membrane fusion in insect cells[J].Virology, 1991, 180(1):395-399.
[65] RAJAH M M, HUBERT M, BISHOP E, et al.SARS-CoV-2 Alpha, Beta, and Delta variants display enhanced Spike-mediated syncytia formation[J].EMBO J, 2021, 40(24):e108944.
[66] KANNO T, ISHIHARA R, HATAMA S, et al.Antigenic variation among recent Japanese isolates of bovine coronaviruses belonging to phylogenetically distinct genetic groups[J].Arch Virol, 2013, 158(5):1047-1053.
[67] GUAN H X, WANG Y W, PERČULIJA V, et al.Cryo-electron microscopy structure of the swine acute diarrhea syndrome coronavirus spike glycoprotein provides insights into evolution of unique coronavirus spike proteins[J].J Virol, 2020, 94(22):e01301-20.
[68] QIAN Z H, OU X Y, GÓES L G B, et al.Identification of the receptor-binding domain of the spike glycoprotein of human betacoronavirus HKU1[J].J Virol, 2015, 89(17):8816-8827.
[69] SZCZEPANSKI A, OWCZAREK K, BZOWSKA M, et al.Canine Respiratory coronavirus, bovine coronavirus, and human coronavirus OC43:receptors and attachment factors[J].Viruses, 2019, 11(4):328.
[70] MILLET J K, JAIMES J A, WHITTAKER G R.Molecular diversity of coronavirus host cell entry receptors[J].FEMS Microbiol Rev, 2021, 45(3):fuaa057.