

Acta Veterinaria et Zootechnica Sinica ›› 2026, Vol. 57 ›› Issue (1): 96-107.doi: 10.11843/j.issn.0366-6964.2026.01.009
• REVIEW • Previous Articles Next Articles
ZHAO Xiumei1(
), ZHAO Haina4, HUA Shu4, CHENG Xu2, CHEN Xiang3, JIANG Yi2(
)
Received:2025-04-09
Online:2026-01-23
Published:2026-01-26
Contact:
JIANG Yi
E-mail:zhao_xiumei@126.com;yijiang620@126.com
CLC Number:
ZHAO Xiumei, ZHAO Haina, HUA Shu, CHENG Xu, CHEN Xiang, JIANG Yi. Research Progress on the Functions of Coronavirus Accessory Proteins[J]. Acta Veterinaria et Zootechnica Sinica, 2026, 57(1): 96-107.
Table 1
The quantity and main functions of coronavirus accessory proteins"
种属 Genera | 病毒 Virus | 数量 Quantity | 主要功能 Main functions |
|---|---|---|---|
| α-CoV | PEDV | 1 | 调节宿主免疫反应与病毒毒力 |
| TGEV | 3 | 调控宿主免疫反应、病毒毒力与组织嗜性 | |
| FIPV | 5 | 调控宿主免疫反应、炎症反应与病毒毒力 | |
| β-CoV | MHV | 4 | 免疫抑制与病毒毒力 |
| MERS-CoV | 5 | 免疫抑制、炎症反应、病毒毒力 | |
| SARS- CoV | 8 | 炎症反应、细胞凋亡、免疫抑制与病毒毒力 | |
| SARS- CoV-2 | 9 | 炎症反应、细胞凋亡、免疫抑制与病毒毒力 | |
| γ-CoV | IBV | 4 | 免疫抑制、发病机理与病毒毒力 |
| δ-CoV | PDCoV | 3 | 免疫抑制与病毒毒力 |
| [1] | ASHOUR H M,ELKHATIB W F,RAHMAN M M,et al.Insights into the recent 2019 novel coronavirus (SARS-CoV-2) in light of past human coronavirus outbreaks[J].Pathogens,2020,9(3):186. |
| [2] | KIRTIPAL N,BHARADWAJ S,KANG S G.From SARS to SARS-CoV-2,insights on structure,pathogenicity and immunity aspects of pandemic human coronaviruses[J].Infect Genet Evol,2020,85:104502. |
| [3] | HOERR F J.The pathology of infectious bronchitis[J].Avian Dis,2021,65(4):600-611. |
| [4] | WILLE M,HOLMES E C.Wild birds as reservoirs for diverse and abundant gamma- and deltacoronaviruses[J].FEMS Microbiol,2020,44:631-644. |
| [5] | LEDNICKY J A,TAGLIAMONTE M S,WHITE S K,et al.Emergence of porcine delta-coronavirus pathogenic infections among children in Haiti through independent zoonoses and convergent evolution[J].Nature,2021,600(7887):133-137. |
| [6] | FANG P,FANG L,ZHANG H,et al.Functions of coronavirus accessory proteins:overview of the state of the art[J].Viruses,2021,13(6):1139. |
| [7] | YOSHIMOTO F K.The proteins of severe acute respiratory syndrome coronavirus-2 (SARS CoV-2 or N-COV19),the cause of COVID-19[J].Protein J,2020,39(3):198-216. |
| [8] | MICHEL C J,MAYER C,POCH O,et al.Characterization of accessory genes in coronavirus genomes[J].Virol J,2020,17(1):131. |
| [9] | LIU D X,FUNG T S,CHONG K K,et al.Accessory proteins of SARS-CoV and other coronaviruses[J].Antiviral Res,2014,109:97-109. |
| [10] | WU A,PENG Y,HUANG B,et al.Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China[J].Cell Host Microbe,2020,27(3):325-328. |
| [11] | TAYLOR R C,CULLEN S P,MARTIN S J.Apoptosis:controlled demolition at the cellular level[J].Nat Rev Mol Cell Biol,2008,9(3):231-41. |
| [12] | PADHAN K,MINAKSHI R,BIN TOWHEED M A,et al.Severe acute respiratory syndrome coronavirus 3a protein activates the mitochondrial death pathway through p38 MAP kinase activation[J].J Gen Virol,2008,89:1960-1969. |
| [13] | TAN Y X,TAN T H,LEE M J,et al.Induction of apoptosis by the severe acute respiratory syndrome coronavirus 7a protein is dependent on its interaction with the Bcl-XL protein[J].J Virol,2007,81:6346-6355. |
| [14] | TAN Y J,FIELDING B C,GOH P Y.Overexpression of 7a,a protein specifically encoded by the severe acute respiratory syndrome coronavirus,induces apoptosis via a caspase-dependent pathway[J].J Virol,2004,78:14043-14047. |
| [15] | YE Z D,WONG C K,LI P,et al.The role of SARS-CoV protein,ORF-6,in the induction of host cell death[J].Hong Kong Med J,2010,16(5 Suppl 4):22-6. |
| [16] | CHEN C Y,PING Y H,LEE H C,et al.Open reading frame 8a of the human severe acute respiratory syndrome coronavirus not only promotes viral replication but also induces apoptosis[J].J Infect Dis,2007,196:405-415. |
| [17] | REN Y,SHU T,WU D,et al.The ORF3a protein of SARS-CoV-2 induces apoptosis in cells[J].Cell Mol Immunol,2020,17:881-883. |
| [18] | VARSHNEY B,AGNIHOTHRAM S,TAN Y J,et al.SARS coronavirus 3b accessory protein modulates transcriptional activity of RUNX1b[J].PLoS One,2012,7(1):e29542. |
| [19] | MINAKSHI R,PADHAN K,RANI M.The SARS coronavirus 3a protein causes endoplasmic reticulum stress and induces ligand-independent downregulation of the type 1 interferon receptor[J].PLoS One,2009,4(12):e8342. |
| [20] | YE Z,WONG C K,LI P,et al.SARS-CoV protein,ORF-6,induces caspase-3 mediated,ER stress and JNK-dependent apoptosis[J].Biochim Biophys Acta,2008,1780(12):1383-1387. |
| [21] | FUNG T S,LIU D X.The ER stress sensor IRE1 and MAP kinase ERK modulate autophagy induction in cells infected with coronavirus infectious bronchitis virus[J].Virology,2019,533:34-44. |
| [22] | FUNG T S,LIAO Y,LIU D X.The endoplasmic reticulum stress sensor IRE1 protects cells from apoptosis induced by the coronavirus infectious bronchitis virus[J].J Virol,2014,88:12752-12764. |
| [23] | ZOU D,XU J,DUAN X,et al.Porcine epidemic diarrhea virus ORF3 protein causes endoplasmic reticulum stress to facilitate autophagy[J].Vet Microbiol,2019,235:209-219. |
| [24] | V’KOVSKI P,KRATZEL A,STEINER S,et al.Coronavirus biology and replication:implications for SARS-CoV-2[J].Nat Rev Microbiol,2021,19(3):155-170. |
| [25] | YOO J S,KATO H,FUJITA T.Sensing viral invasion by RIG-I like receptors[J].Curr Opin Microbiol,2014,20:131-138. |
| [26] | SIU K L,YEUNG M L,KOK K H.Middle east respiratory syndrome coronavirus 4a protein is a double-stranded RNA-binding protein that suppresses PACT-induced activation of RIG-I and MDA5 in the innate antiviral response[J].J Virol,2014,88:4866-4876. |
| [27] | FANG P,FANG L,REN J,et al.Porcine deltacoronavirus accessory protein NS6 antagonizes interferon beta production by interfering with the binding of RIG-I/MDA5 to double-Stranded RNA[J].J Virol,2018,92(15):e00712-18. |
| [28] | XIAO X,FU Y,YOU W.Inhibition of the RLR signaling pathway by SARS-CoV-2 ORF7b is mediated by MAVS and abrogated by ORF7b-homologous interfering peptide[J].J Virol,2024,98(5):e0157323. |
| [29] | LI X,HOU P,MA W.SARS-CoV-2 ORF10 suppresses the antiviral innate immune response by degrading MAVS through mitophagy[J].Cell Mol Immunol,2022,19(1):67-78. |
| [30] | SHI C S,QI H Y.SARS-Coronavirus open reading frame-9b suppresses innate immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 signalosome[J].J Immunol,2014,193:3080-3089. |
| [31] | GAO X,ZHU K,QIN B.Crystal structure of SARS-CoV-2 ORF9b in complex with human TOM70 suggests unusual virus-host interactions[J].Nat Commun,2021,12(1):2843. |
| [32] | WU J,SHI Y,PAN X.SARS-CoV-2 ORF9b inhibits RIG-I-MAVS antiviral signaling by interrupting K63-linked ubiquitination of NEMO[J].Cell Rep,2021,34(7):108761. |
| [33] | NIE Y,MOU L,LONG Q.SARS-CoV-2 ORF3a positively regulates NF-κB activity by enhancing IKKβ- NEMO interaction[J].Virus Res,2023,328:199086. |
| [34] | RUI Y,SHEN S,WANG Y,et al.HIV-1 vpu and SARS-CoV-2 ORF3a proteins disrupt STING-mediated activation of antiviral NF-κB signaling[J].Sci Signal,2025,18(870):eadd6593. |
| [35] | FANG P,FANG L,XIA S.Porcine deltacoronavirus accessory protein NS7a antagonizes IFN-β production by competing with TRAF3 and IRF3 for binding to IKKε[J].Front Cell Infect Microbiol,2020,10:257. |
| [36] | YANG Y,YE F,ZHU N,et al.Middle east respiratory syndrome coronavirus ORF4b protein inhibits type I interferon production through both cytoplasmic and nuclear targets[J].Sci Rep,2015,5:17554. |
| [37] | WONG L R,YE Z W,LUI P Y,et al.Middle east respiratory syndrome coronavirus ORF8b accessory protein suppresses type I IFN expression by impeding HSP70-dependent activation of IRF3 kinase IKKepsilon[J].J Immunol,2020,205:1564-1579. |
| [38] | WONG H H,FUNG T S,FANG S,et al.Accessory proteins 8b and 8ab of severe acute respiratory syndrome coronavirus suppress the interferon signaling pathway by mediating ubiquitin-dependent rapid degradation of interferon regulatory factor 3[J].Virology,2018,515:165-175. |
| [39] | CANTON J,FEHR A R,FERNANDEZ-DELGADO R,et al.MERS-CoV 4b protein interferes with the NF-kappaB-dependent innate immune response during infection[J].PLoS Pathog,2018,14(1):e1006838. |
| [40] | ZHANG Q,SHI K,YOO D.Suppression of type I interferon production by porcine epidemic diarrhea virus and degradation of CREB-binding protein by nsp1[J].Virology,2016,489:252-68. |
| [41] | ZHENG L,LIU H,TIAN Z.Porcine epidemic diarrhea virus (PEDV) ORF3 protein inhibits cellular type I interferon signaling through down-regulating proteins expression in RLRs-mediated pathway[J].Res Vet Sci,2023,159:146-159. |
| [42] | LEI X,DONG X,MA R.Activation and evasion of type I interferon responses by SARS-CoV-2[J].Nat Commun,2020,11(1):3810. |
| [43] | CHEN J,LU Z,YANG X.Severe acute respiratory syndrome coronavirus 2 ORF8 protein inhibits type I interferon production by targeting HSP90B1 signaling[J].Front Cell Infect Microbiol,2022,12:899546. |
| [44] | CHENG W,CHEN S,LI R.Severe acute respiratory syndrome coronavirus protein 6 mediates ubiquitin-dependent proteosomal degradation of N-Myc (and STAT) interactor[J].Virol Sin,2015,30(2):153-161. |
| [45] | WANG J,YANG B,HU Y,et al.Negative regulation of Nmi on virus-triggered type I IFN production by targeting IRF7[J].J Immunol,2013,191(6):3393-3399. |
| [46] | MIORIN L,KEHRER T,SANCHEZ-APARICIO M T,et al.SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling[J].Proc Nat Acad Sci USA,2020,117(45):28344-28354. |
| [47] | XIA H,CAO Z,XIE X,et al.Evasion of type I interferon by SARS-CoV-2[J].Cell Rep,2020,33(1):108234. |
| [48] | BEIDAS M,CHEHADEH W.Effect of human coronavirus OC43 structural and accessory proteins on the transcriptional activation of antiviral response elements[J].Intervirology,2018,61(1):30-35. |
| [49] | YANG Y,ZHANG L,GENG H,et al.The structural and accessory proteins M,ORF 4a,ORF 4b,and ORF 5 of middle east respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists[J].Protein Cell,2013,4(12):951-961. |
| [50] | LU Y,SU X,DU C.Genetic diversity of porcine epidemic diarrhea virus with a naturally occurring truncated ORF3 gene found in Guangxi,China[J].Front Vet Sci,2020,7:435. |
| [51] | ZHANG Y H,LI H X,CHEN X M.Genetic characteristics and pathogenicity of a novel porcine epidemic diarrhea virus with a naturally occurring truncated ORF3 gene[J].Viruses,2022,14(3):487. |
| [52] | HAIJEMA B J,VOLDERS H,ROTTIER P J M.Live,attenuated coronavirus vaccines through the directed deletion of group-specific genes provide protection against feline infectious peritonitis[J].J Virol,2004,78:3863-3871. |
| [53] | DEDEURWAERDER A,DESMARETS L M,OLYSLAEGERS D A.The role of accessory proteins in the replication of feline infectious peritonitis virus in peripheral blood monocytes[J].Vet Microbiol,2013,162:447-455. |
| [54] | CRUZ J L,SOLA I,BECARES M.Coronavirus gene 7 counteracts host defenses and modulates virus virulence[J].PLoS Pathog,2011,7(6):e1002090. |
| [55] | ISSA E,MERHI G,PANOSSIAN B,et al.SARS-CoV-2 and ORF3a:nonsynonymous mutations,functional domains,and viral pathogenesis[J].mSystems,2020,5(3):e00266-20. |
| [56] | HASSAN S S,CHOUDHURY P P,BASU P,et al.Molecular conservation and differential mutation on ORF3a gene in Indian SARS-CoV2 genomes[J].Genomics,2020,112(5):3226-3237. |
| [57] | HASSAN S S,ATTRISH D,GHOSH S,et al.Pathogenic perspective of missense mutations of ORF3a protein of SARS-CoV-2[J]. Virus Res,2021,300:198441. |
| [58] | SILVAS J A,VASQUEZ D M,PARK J G,et al.Contribution of SARS-CoV-2 accessory proteins to viral pathogenicity in K18 human ACE2 transgenic mice[J].J Virol,2021,95(17):e0040221. |
| [59] | YOUNG B E,FONG S W,CHAN Y H,et al.Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response:an observational cohort study[J].Lancet,2020,396(10251):603-611. |
| [60] | LIU Y,ZHANG X,LIU J.A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions[J]. Nat Commun,2022,13(1):4337. |
| [61] | BELLO-PEREZ M,HURTADO-TAMAYO J,MYKYTYN A Z.SARS-CoV-2 ORF8 accessory protein is a virulence factor[J].mBio,2023,14(5):e0045123. |
| [62] | PEWE L,ZHOU H,NETLAND J,et al.A severe acute respiratory syndrome-associated coronavirus-specific protein enhances virulence of an attenuated murine coronavirus[J].J Virol,2005,79(17):11335-11342. |
| [63] | DE HAAN C A,MASTERS P S,SHEN X,et al.The group-specific murine coronavirus genes are not essential,but their deletion,by reverse genetics,is attenuating in the natural host[J].Virology,2002,296(1):177-189. |
| [64] | MENACHERY V D,MITCHELL H D,COCKRELL A S.MERS-CoV accessory ORFs play key role for infection and pathogenesis[J].mBio,2017,8(4):e00665-17. |
| [65] | LI Y,JIN Y,KUANG L.The N-terminal region of middle east respiratory syndrome coronavirus accessory protein 8b is essential for enhanced virulence of an attenuated murine coronavirus[J].J Virol,2022,96(3):e0184221. |
| [66] | VAN BEURDEN S J,BERENDS A J,KRÄMER-KÜHL A,et al.Recombinant live attenuated avian coronavirus vaccines with deletions in the accessory genes 3ab and/or 5ab protect against infectious bronchitis in chickens[J].Vaccine,2018,36 (8):1085-1092. |
| [67] | LACONI A,VAN BEURDEN S J,BERENDS A J,et al.Deletion of accessory genes 3a,3b,5a or 5b from avian coronavirus infectious bronchitis virus induces an attenuated phenotype both in vitro and in vivo[J].J Gen Virol,2018,99 (10):1381-1390. |
| [68] | ZHAO X,JIANG Y,CHENG X,et al.Pathogenicity of a QX-like strain of infectious bronchitis virus and effects of accessory proteins 3a and 3b in chickens[J].Vet Microbiol,2019,239 (4):108-114. |
| [69] | ZHAO Y,CHENG J,YAN S,et al.S gene and 5a accessory gene are responsible for the attenuation of virulent infectious bronchitis coronavirus[J].Virology,2019,533 (2):12-20. |
| [70] | ZHANG M,LI W,ZHOU P,et al.Genetic manipulation of porcine deltacoronavirus reveals insights into NS6 and NS7 functions:a novel strategy for vaccine design[J].Emerg Microbes Infect,2019,9(1):20-31. |
| [71] | YE C,PARK J G,CHIEM K.Immunization with recombinant accessory protein-deficient SARS-CoV-2 protects against lethal challenge and viral transmission[J]. Microbiol Spectr,2023,11(3):e0065323. |
| [72] | ZHANG C,GERZANICH V,CRUZ-COSME R,et al.SARS-CoV-2 ORF3a induces COVID-19-associated kidney injury through HMGB1-mediated cytokine production[J].mBio,2024,15(11):e0230824. |
| [73] | ZHANG J,HOM K,ZHANG C.SARS-CoV-2 ORF3a protein as a therapeutic target against COVID-19 and long-term post-infection effects[J].Pathogens,2024,13(1):75. |
| [74] | ZHANG Y,CHEN Y,LI Y.The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-Ι[J].Proc Natl Acad Sci U S A,2021,118(23):e2024202118. |
| [75] | ZINZULA L.Lost in deletion:the enigmatic ORF8 protein of SARS-CoV-2[J].Biochem Biophys Res Commun,2021,538:116-124. |
| [76] | JIANG H W,ZHANG H N,MENG Q F.SARS-CoV-2 Orf9b suppresses type I interferon responses by targeting TOM70[J].Cell Mol Immunol,2020,17(9):998-1000. |
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