动物疱疹病毒pUL7的生物学功能

doi:10.11843/j.issn.0366-6964.2025.12.010

摘要/Abstract

摘要： UL7基因在疱疹病毒科成员中高度保守，其编码的pUL7蛋白在病毒感染的致病调控过程中发挥着关键的生物学作用。本文梳理了UL7基因编码蛋白的结构特征，并全面总结了pUL7在病毒复制、转录、蛋白表达、病毒粒子组装与释放等生命周期关键阶段的功能，同时探讨了其与其他病毒及宿主蛋白的相互作用机制，旨在为疱疹病毒UL7基因的深入研究提供参考。

关键词: 疱疹病毒, pUL7, 蛋白结构, 功能

Abstract: The UL7 gene is highly conserved among members of the Herpesviridae family, and its encoded pUL7 protein plays a critical biological role in the pathogenic regulation of viral infection. This review systematically outlines the structural characteristics of the UL7-encoded protein and comprehensively summarizes the functions of pUL7 in key stages of the viral life cycle, including review systematically summarizes the structural characteristics of UL7-encoded proteins and the replication, transcription, protein expression, virion assembly, and release. Additionally, it explores the interaction mechanisms between pUL7 and other viral or host proteins, aiming to provide valuable insights for further research on the UL7 gene in herpesviruses.

Key words: herpes virus, UL7 protein, protein structure, function

中图分类号:

S852.659.1

兰星, 汪铭书, 程安春. 动物疱疹病毒pUL7的生物学功能[J]. 畜牧兽医学报, 2025, 56(12): 6046-6059.

LAN Xing, WANG Mingshu, CHENG Anchun. Biological Functions of the Animal Herpesvirus pUL7[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(12): 6046-6059.

参考文献

[1] OWEN D J, CRUMP C M, GRAHAM S C. Tegument assembly and secondary envelopment of alphaherpesviruses [J]. Viruses, 2015, 7(9): 5084-5114.
[2] KELLY B J, FRAEFEL C, CUNNINGHAM A L, et al. Functional roles of the tegument proteins of herpes simplex virus type 1 [J]. Virus Res, 2009, 145(2): 173-186.
[3] ZERBONI L, SEN N, OLIVER S L, et al. Molecular mechanisms of varicella zoster virus pathogenesis [J]. Nat Rev Microbiol, 2014, 12(3): 197-210.
[4] ISHIHARA R, WATANABE R, SHIOMI M, et al. Exploring the link between varicella-zoster virus, autoimmune diseases, and the role of recombinant zoster vaccine [J]. Biomolecules, 2024, 14(7):739.
[5] NIU Q, ZHOU C, LI R, et al. Proteomic analysis reveals the antiviral effects of baicalin on pseudorabies virus [J]. Int J Biol Macromol, 2024, 277(Pt 1): 134149.
[6] FAZEL F, MATSUYAMA-KATO A, ALIZADEH M, et al. A Marek's disease virus messenger RNA-based vaccine modulates local and systemic immune responses in chickens [J]. Viruses, 2024, 16(7):1156.
[7] KOUR J, RAI T S, KAUR G, et al. Prevalence of bovine herpes virus-1 among reproductive disorders in cattle and buffaloes in Punjab region of India [J]. Virus Dis, 2024, 35(2): 338-341.
[8] WAN J, WANG M, CHENG A, et al. Identification and subcellular localization of proteins that interact with duck plague virus pUL14 in infected host cells [J]. Poult Sci, 2024, 104(1): 104649.
[9] ADAM O, OLADELE O A, YIMAM T M, et al. Serological and molecular detection of infectious laryngotracheitis virus in chickens in Central Gondar Zone, Ethiopia [J]. Front Vet Sci, 2025, 12: 1517373.
[10] LUJAN E, ZHANG I, GARON A C, et al. The interactions of the complement system with human cytomegalovirus [J]. Viruses, 2024, 16(7):1171.
[11] HEYN I, BREMER L, ZINGLER P, et al. Self-repairing herpesvirus saimiri deletion variants [J]. Viruses, 2022, 14(7):1525.
[12] ZHEN J, CHEN J, HUANG H, et al. Structures of Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus virions reveal species-specific tegument and envelope features [J]. J Virol, 2024, 98(11): e0119424.
[13] DRY I, TODD H, DEANE D, et al. Alcelaphine herpesvirus 1 glycoprotein B: recombinant expression and antibody recognition [J]. Arch Virol, 2016, 161(3): 613-619.
[14] DAMANIA B, KENNEY S C, RAAB-TRAUB N. Epstein-Barr virus: Biology and clinical disease [J]. Cell, 2022, 185(20): 3652-3670.
[15] AHMAD I, WILSON D W. HSV-1 Cytoplasmic envelopment and egress [J]. Int J Mol Sci, 2020, 21(17):5969.
[16] NEWCOMB W W, JUHAS R M, THOMSEN D R, et al. The UL6 gene product forms the portal for entry of DNA into the herpes simplex virus capsid [J]. J Virol, 2001, 75(22): 10923-10932.
[17] ZHOU Z H, DOUGHERTY M, JAKANA J, et al. Seeing the herpesvirus capsid at 8.5 A [J]. Science, 2000, 288(5467): 877-880.
[18] NEWCOMB W W, BOOY F P, BROWN J C. Uncoating the herpes simplex virus genome [J]. J Mol Biol, 2007, 370(4): 633-642.
[19] NEWCOMB W W, JONES L M, DEE A, et al. Role of a reducing environment in disassembly of the herpesvirus tegument [J]. Virology, 2012, 431(1-2): 71-79.
[20] LORET S, GUAY G, LIPPÉ R. Comprehensive characterization of extracellular herpes simplex virus type 1 virions [J]. J Virol, 2008, 82(17): 8605-8618.
[21] LORET S, LIPPÉ R. Biochemical analysis of infected cell polypeptide (ICP)0, ICP4, UL7 and UL23 incorporated into extracellular herpes simplex virus type 1 virions [J]. J Gen Virol, 2012, 93(Pt 3): 624-634.
[22] 李艺璇, 牛静轶, 李港, 等. 伪狂犬病病毒编码的内膜蛋白生物学功能研究进展[J]. 畜牧兽医学报, 2024, 55(3): 957-970.
LI Y X, NIU J Y, LI G, et al. Research progress on the biological functions of tegument proteins encoded by pseudorabies virus[J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(3): 957-970. (in Chinese)
[23] TANAKA M, SATA T, KAWAGUCHI Y. The product of the herpes simplex virus 1 UL7 gene interacts with a mitochondrial protein, adenine nucleotide translocator 2 [J]. Virol J, 2008, 5: 125.
[24] MACMANIMAN J D, MEUSER A, BOTTO S, et al. Human cytomegalovirus-encoded pUL7 is a novel CEACAM1-like molecule responsible for promotion of angiogenesis [J]. mBio, 2014, 5(6):e02035.
[25] GRüNEWALD K, DESAI P, WINKLER D C, et al. Three-dimensional structure of herpes simplex virus from cryo-electron tomography [J]. Science, 2003, 302(5649): 1396-1398.
[26] RADTKE K, KIENEKE D, WOLFSTEIN A, et al. Plus- and minus-end directed microtubule motors bind simultaneously to herpes simplex virus capsids using different inner tegument structures [J]. PLoS Pathog, 2010, 6(7): e1000991.
[27] WOLFSTEIN A, NAGEL C H, RADTKE K, et al. The inner tegument promotes herpes simplex virus capsid motility along microtubules in vitro [J]. Traffic, 2006, 7(2): 227-237.
[28] SHIBAZAKI M, KATO A, TAKESHIMA K, et al. Phosphoregulation of a conserved herpesvirus tegument protein by a virally encoded protein kinase in viral pathogenicity and potential linkage between its evolution and viral phylogeny [J]. J Virol, 2020, 94(18):e01055-20.
[29] ORTIZ D A, GLASSBROOK J E, PELLETT P E. Protein-protein interactions suggest novel activities of human cytomegalovirus tegument protein pUL103 [J]. J Virol, 2016, 90(17): 7798-7810.
[30] BUTNARU M, GAGLIA M M. The Kaposi's sarcoma-associated herpesvirus protein ORF42 is required for efficient virion production and expression of viral proteins [J]. Viruses, 2019, 11(8):711.
[31] FUNK C, RASCHBICHLER V, LIEBER D, et al. Comprehensive analysis of nuclear export of herpes simplex virus type 1 tegument proteins and their Epstein-Barr virus orthologs[J]. Traffic, 2019, 20(2):152-167.
[32] JOHANNSEN E, LUFTIG M, CHASE M R, et al. Proteins of purified Epstein-Barr virus [J]. Proc Natl Acad Sci U S A, 2004, 101(46): 16286-16291.
[33] VARNUM S M, STREBLOW D N, MONROE M E, et al. Identification of proteins in human cytomegalovirus (HCMV) particles: the HCMV proteome [J]. J Virol, 2004, 78(20): 10960-10966.
[34] ZHANG Z, SELARIU A, WARDEN C, et al. Genome-wide mutagenesis reveals that ORF7 is a novel VZV skin-tropic factor [J]. PLoS Pathog, 2010, 6(7): e1000971.
[35] FAN D, WANG M, CHENG A, et al. The role of VP16 in the life cycle of alphaherpesviruses [J]. Front Microbiol, 2020, 11: 1910.
[36] GAO L, LIU R, YANG F, et al. Duck enteritis virus inhibits the cGAS-STING DNA-sensing pathway to evade the innate immune response [J]. J Virol, 2022, 96(24): e0157822.
[37] HE T, WANG M, CHENG A, et al. Duck plague virus UL41 protein inhibits RIG-I/MDA5-mediated duck IFN-β production via mRNA degradation activity [J]. Vet Res, 2022, 53(1): 22.
[38] ZHOU L, CHENG A, WANG M, et al. Mechanism of herpesvirus protein kinase UL13 in immune escape and viral replication [J]. Front Immunol, 2022, 13: 1088690.
[39] DIEFENBACH R J. Conserved tegument protein complexes: Essential components in the assembly of herpesviruses [J]. Virus Res, 2015, 210: 308-317.
[40] CHANG H, CHENG A, WANG M, et al. Immunofluorescence analysis of duck plague virus gE protein on DPV-infected ducks [J]. Virol J, 2011, 8: 19.
[41] LIU C, CHENG A, WANG M, et al. Duck enteritis virus UL54 is an IE protein primarily located in the nucleus [J]. Virol J, 2015, 12: 198.
[42] ZHOU T, WANG M, RUAN P, et al. Research note: Duck plague virus pUL48 is a late protein that plays an important role in viral replication [J]. Poult Sci, 2023, 102(2): 102358.
[43] DUNN L E M, BIRKENHEUER C H, BAINES J D. A revision of herpes simplex virus type 1 transcription: first, repress; then, express [J]. Microorganisms, 2024, 12(2):262.
[44] GRUFFAT H, MARCHIONE R, MANET E. Herpesvirus late gene expression: A viral-specific pre-initiation complex is key [J]. Front Microbiol, 2016, 7: 869.
[45] PATEL A H, MACLEAN J B. The product of the UL6 gene of herpes simplex virus type 1 is associated with virus capsids [J]. Virology, 1995, 206(1): 465-478.
[46] XU X L， FENG X, WANG L C, et al. A HSV1 mutant leads to an attenuated phenotype and induces immunity with a protective effect [J]. PLoS Pathog, 2020, 16(8): e1008703.
[47] NOZAWA N, DAIKOKU T, YAMAUCHI Y, et al. Identification and characterization of the UL7 gene product of herpes simplex virus type 2 [J]. Virus Genes, 2002, 24(3): 257-266.
[48] WANG W, FU W, PAN D, et al. Varicella-zoster virus ORF7 interacts with ORF53 and plays a role in its trans-Golgi network localization [J]. Virol Sin, 2017, 32(5): 387-395.
[49] FUCHS W, GRANZOW H, KLOPFLEISCH R, et al. The UL7 gene of pseudorabies virus encodes a nonessential structural protein which is involved in virion formation and egress [J]. J Virol, 2005, 79(17): 11291-11299.
[50] SCHMITT J, KEIL G M. Identification and characterization of the bovine herpesvirus 1 UL7 gene and gene product which are not essential for virus replication in cell culture [J]. J Virol, 1996, 70(2): 1091-1099.
[51] PASDELOUP D, CHUARD A, RÉMY S, et al. The pUL51 tegument protein is essential for Marek's disease virus growth in vitro and bears a function that is critical for pathogenesis in vivo [J]. J Virol, 2023, 97(5): e0024223.
[52] HUANG J, WANG M S, CHENG A C, et al. Duck enteritis virus UL7 is a late gene and the UL7-encoded protein co-localizes with pUL51 [J]. Acta Virol, 2024, 68：12023.
[53] MAHMOUDIAN A, MARKHAM P F, NOORMOHAMMADI A H, et al. Kinetics of transcription of infectious laryngotracheitis virus genes [J]. Comp Immunol Microbiol Infect Dis, 2012, 35(2): 103-15.
[54] AHLQVIST J, MOCARSKI E. Cytomegalovirus UL103 controls virion and dense body egress [J]. J Virol, 2011, 85(10): 5125-5135.
[55] CHAMBERS J, ANGULO A, AMARATUNGA D, et al. DNA microarrays of the complex human cytomegalovirus genome: profiling kinetic class with drug sensitivity of viral gene expression [J]. J Virol, 1999, 73(7): 5757-5766.
[56] CHEE M S, BANKIER A T, BECK S, et al. Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169 [J]. Curr Top Microbiol Immunol, 1990, 154: 125-169.
[57] BAER R, BANKIER A T, BIGGIN M D, et al. DNA sequence and expression of the B95-8 Epstein-Barr virus genome [J]. Nature, 1984, 310(5974): 207-211.
[58] KURIYAMA K, WATANABE T, OHNO S. Analysis of the interaction between the ORF42 and ORF55 proteins encoded by Kaposi's sarcoma-associated herpesvirus [J]. Arch Virol, 2024, 169(5): 98.
[59] KWAN K Y, WANG J C. Mice lacking DNA topoisomerase IIIbeta develop to maturity but show a reduced mean lifespan [J]. Proc Natl Acad Sci U S A, 2001, 98(10): 5717-5721.
[60] XU X, FAN S, ZHOU J, et al. The mutated tegument protein UL7 attenuates the virulence of herpes simplex virus 1 by reducing the modulation of α-4 gene transcription [J]. Virol J, 2016, 13(1): 152.
[61] DAS S, ORTIZ D A, GURCZYNSKI S J, et al. Identification of human cytomegalovirus genes important for biogenesis of the cytoplasmic virion assembly complex [J]. J Virol, 2014, 88(16): 9086-9099.
[62] BORTZ E, WHITELEGGE J P, JIA Q, et al. Identification of proteins associated with murine gammaherpesvirus 68 virions [J]. J Virol, 2003, 77(24): 13425-13432.
[63] KATTENHORN L M, MILLS R, WAGNER M, et al. Identification of proteins associated with murine cytomegalovirus virions [J]. J Virol, 2004, 78(20): 11187-11197.
[64] KRAMER T, GRECO T M, ENQUIST L W, et al. Proteomic characterization of pseudorabies virus extracellular virions [J]. J Virol, 2011, 85(13): 6427-6441.
[65] VIDICK S, LEROY B, PALMEIRA L, et al. Proteomic characterization of murid herpesvirus 4 extracellular virions [J]. PloS One, 2013, 8(12): e83842.
[66] ZHU F X, CHONG J M, WU L, et al. Virion proteins of Kaposi's sarcoma-associated herpesvirus [J]. J Virol, 2005, 79(2): 800-811.
[67] GUO H, SHEN S, WANG L, et al. Role of tegument proteins in herpesvirus assembly and egress [J]. Protein Cell, 2010, 1(11): 987-998.
[68] KALEJTA R F. Functions of human cytomegalovirus tegument proteins prior to immediate early gene expression [J]. Curr Top Microbiol Immunol, 2008, 325: 101-115.
[69] KALEJTA R F. Tegument proteins of human cytomegalovirus [J]. Microbiol Mol Biol Rev, 2008, 72(2): 249-265.
[70] SMITH R M, KOSURI S, KERRY J A. Role of human cytomegalovirus tegument proteins in virion assembly [J]. Viruses, 2014, 6(2): 582-605.
[71] WANG W, CHENG T, ZHU H, et al. Insights into the function of tegument proteins from the varicella zoster virus [J]. Sci China Life Sci, 2015, 58(8): 739-749.
[72] BIGALKE J M, HELDWEIN E E. Nuclear exodus: Herpesviruses lead the way [J]. Annu Rev Virol, 2016, 3(1): 387-409.
[73] HEMING J D, CONWAY J F, HOMA F L. Herpesvirus capsid assembly and DNA packaging [J]. Adv Anat Embryol Cell Biol, 2017, 223: 119-142.
[74] EISENBERG R J, ATANASIU D, CAIRNS T M, et al. Herpes virus fusion and entry: a story with many characters [J]. Viruses, 2012, 4(5): 800-832.
[75] ALBECKA A, OWEN D J, IVANOVA L, et al. Dual function of the pUL7-pUL51 tegument protein complex in herpes simplex virus 1 infection [J]. J Virol, 2017, 91(2):e02196-16.
[76] CARY L A, GUAN J L. Focal adhesion kinase in integrin-mediated signaling [J]. Front Biosci, 1999, 4: D102- D113.
[77] PARSONS J T, HORWITZ A R, SCHWARTZ M A. Cell adhesion: integrating cytoskeletal dynamics and cellular tension [J]. Nat Rev Mol Cell Biol, 2010, 11(9): 633-643.
[78] FEUTZ E, MCLELAND-WIESER H, MA J L, et al. Functional interactions between herpes simplex virus pUL51, pUL7 and gE reveal cell-specific mechanisms for epithelial cell-to-cell spread [J]. Virology, 2019, 537: 84-96.
[79] BUTT B G, OWEN D J, JEFFRIES C M, et al. Insights into herpesvirus assembly from the structure of the pUL7:pUL51 complex [J]. Elife, 2020, 9:e53789.
[80] HE H P, LUO M, CAO Y L, et al. Structure of Epstein-Barr virus tegument protein complex BBRF2-BSRF1 reveals its potential role in viral envelopment [J]. Nat Commun, 2020, 11(1): 5405.
[81] BARDENS A, DÖRING T, STIELER J, et al. Alix regulates egress of hepatitis B virus naked capsid particles in an ESCRT-independent manner [J]. Cell Microbiol, 2011, 13(4): 602-619.
[82] LEE C P, LIU P T, KUNG H N, et al. The ESCRT machinery is recruited by the viral BFRF1 protein to the nucleus-associated membrane for the maturation of Epstein-Barr virus [J]. PLoS Pathog, 2012, 8(9): e1002904.
[83] STRECK N T, ZHAO Y, SUNDSTROM J M, et al. Human cytomegalovirus utilizes extracellular vesicles to enhance virus spread [J]. J Virol, 2020, 94(16): e00609-20.
[84] TURNER D L, KORNEEV D V, PURDY J G, et al. The host exosome pathway underpins biogenesis of the human cytomegalovirus virion [J]. Elife, 2020, 9:e58288.
[85] REYNOLDS A E, WILLS E G, ROLLER R J, et al. Ultrastructural localization of the herpes simplex virus type 1 UL31, UL34, and US3 proteins suggests specific roles in primary envelopment and egress of nucleocapsids [J]. J Virol, 2002, 76(17): 8939-8952.
[86] RYCKMAN B J, ROLLER R J. Herpes simplex virus type 1 primary envelopment: UL34 protein modification and the US3-UL34 catalytic relationship [J]. J Virol, 2004, 78(1): 399-412.
[87] ROLLER R J, FETTERS R. The herpes simplex virus 1 UL51 protein interacts with the UL7 protein and plays a role in its recruitment into the virion [J]. J Virol, 2015, 89(6): 3112-3122.
[88] NOZAWA N, DAIKOKU T, KOSHIZUKA T, et al. Subcellular localization of herpes simplex virus type 1 UL51 protein and role of palmitoylation in Golgi apparatus targeting [J]. J Virol, 2003, 77(5): 3204-3216.
[89] ORZALLI M H, BROEKEMA N M, DINER B A, et al. cGAS-mediated stabilization of IFI16 promotes innate signaling during herpes simplex virus infection [J]. Proc Natl Acad Sci U S A, 2015, 112(14): E1773-E1781.
[90] KONISHI N, NARITA Y, HIJIOKA F, et al. BGLF2 increases infectivity of Epstein-Barr virus by activating AP-1 upon de novo infection [J]. mSphere, 2018, 3(2):e00138-18.
[91] MASUD H, YANAGI Y, WATANABE T, et al. Epstein-Barr virus BBRF2 is required for maximum infectivity [J]. Microorganisms, 2019, 7(12):705.
[92] XU X, GUO Y, FAN S, et al. Attenuated phenotypes and analysis of a herpes simplex virus 1 strain with partial deletion of the UL7, UL41 and LAT genes [J]. Virol Sin, 2017, 32(5): 404-414.
[93] FAN S T, XU X L, LIAO Y, et al. Attenuated phenotype and immunogenic characteristics of a mutated herpes simplex virus 1 strain in the rhesus macaque [J]. Viruses, 2018, 10(5):234.
[94] XU X L, HE Y F, FAN S T, et al. Reducing viral inhibition of host cellular apoptosis strengthens the immunogenicity and protective efficacy of an attenuated HSV-1 strain [J]. Virol Sin, 2019, 34(6): 673-787.
[95] RAUCH S, JASNY E, SCHMIDT K E, et al. New vaccine technologies to combat outbreak situations [J]. Front Immunol, 2018, 9: 1963.
[96] DING C, SUN Y, ZHANG X, et al. The immunogenicity of PRV ΔgE/TK/UL49.5 three-gene-deleted vaccine in mice [J]. Virol J, 2025, 22(1): 25.
[97] NING Y, HUANG Y, WANG M, et al. Evaluation of the Safety and Immunogenicity of Duck-Plague Virus gE Mutants [J]. Front Immunol, 2022, 13: 882796.
[98] TANG A, ZHU M, ZHU J, et al. Pathogenicity and immunogenicity of gI/gE/TK-gene-deleted felid herpesvirus 1 variants in cats [J]. Virol J, 2023, 20(1): 87.