甲型疱疹病毒亚科的疱疹病毒囊膜糖蛋白gC对病毒感染复制的影响

doi:10.11843/j.issn.0366-6964.2022.09.005

摘要/Abstract

摘要： 甲型疱疹病毒亚科的疱疹病毒宿主广泛，能感染哺乳类、两栖类和禽类，主要侵害宿主的皮肤、黏膜和神经组织，病毒还会在宿主神经组织潜伏感染，一经感染，难以清除。gC是甲型疱疹病毒亚科的病毒囊膜糖蛋白之一，在病毒感染复制过程中发挥了重要作用。gC与细胞上受体结合帮助病毒吸附至宿主细胞表面、介导低pH条件下病毒入侵上皮细胞、影响病毒基因组的复制。此外，gC帮助病毒逃避补体和抗体的中和，促进病毒的吸附入侵。本文就gC影响病毒感染复制的相关功能进行综述，旨在为研究gC和深入了解甲型疱疹病毒亚科病毒的生命周期，以及gC亚单位疫苗和mRNA疫苗的研究提供参考。

关键词: 甲型疱疹病毒亚科, gC, 吸附, 水平传播, 免疫逃避

Abstract: Alpha herpesvirus has a wide range of hosts, and can infect mammals, amphibians and poultry. It mainly invades the skin, mucous membrane and nerve tissue of the host and latently infects the nerve tissue of the host. Once infected, it is difficult to be eradicated. gC is one of the envelope glycoproteins of alpha herpesvirus, which plays an important role in the process of viral infection and replication. gC binds to receptors on the cell to help the virus adsorb to the surface of the host, mediates the invasion of the virus into epithelial cells at low pH, and affects the replication of the viral genome. In addition, gC helps the virus evade the neutralization of complement and antibodies, and promotes the absorption and invasion of the virus. In this review, the related functions of gC affecting viral infection and replication were reviewed to provide reference for the study of gC and the life cycle of the alpha herpesvirus, as well as the research of gC subunit vaccine and mRNA vaccine.

Key words: alpha herpesvirus, gC, adsorption, horizontal transmission, immune evasion

中图分类号:

S852.659.1

丰鑫, 汪铭书, 程安春. 甲型疱疹病毒亚科的疱疹病毒囊膜糖蛋白gC对病毒感染复制的影响[J]. 畜牧兽医学报, 2022, 53(9): 2867-2876.

FENG Xin, WANG Mingshu, CHENG Anchun. The Role of Alpha Herpesvirus Envelope Glycoprotein C on Virus Infection and Replication[J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(9): 2867-2876.

参考文献 89

[1]	MCGEOCH D J, RIXON F J, DAVISON A J. Topics in herpesvirus genomics and evolution[J]. Virus Res, 2006, 117(1):90-104.
[2]	METTENLEITER T C, KLUPP B G, GRANZOW H. Herpesvirus assembly:a tale of two membranes[J]. Curr Opin Microbiol, 2006, 9(4):423-429.
[3]	LAQUERRE S, ARGNANI R, ANDERSON D B, et al. Heparan sulfate proteoglycan binding by herpes simplex virus type 1 glycoproteins B and C, which differ in their contributions to virus attachment, penetration, and cell-to-cell spread[J]. J Virol, 1998, 72(7):6119-6130.
[4]	FEYZI E, TRYBALA E, BERGSTRÖM T, et al. Structural requirement of heparan sulfate for interaction with herpes simplex virus type 1 virions and isolated glycoprotein C[J]. J Biol Chem, 1997, 272(40):24850-24857.
[5]	THUREEN D R, KEELER C L JR. Psittacid herpesvirus 1 and infectious laryngotracheitis virus:Comparative genome sequence analysis of two avian alphaherpesviruses[J]. J Virol, 2006, 80(16):7863-7872.
[6]	TRYBALA E, ROTH A, JOHANSSON M, et al. Glycosaminoglycan-binding ability is a feature of wild-type strains of herpes simplex virus Type 1[J]. Virology, 2002, 302(2):413-419.
[7]	DAVISON A J. Evolution of sexually transmitted and sexually transmissible human herpesviruses[J]. Ann NY Acad Sci, 2011, 1230(1):E37-E49.
[8]	SCHWYZER M, ACKERMANN M. Molecular virology of ruminant herpesviruses[J]. Vet Microbiol, 1996, 53(1-2):17-29.
[9]	KLUPP B G, HENGARTNER C J, METTENLEITER T C, et al. Complete, annotated sequence of the pseudorabies virus genome[J]. J Virol, 2004, 78(1):424-440.
[10]	TULMAN E R, AFONSO C L, LU Z, et al. The genome of a very virulent Marek's disease virus[J]. J Virol, 2000, 74(17):7980-7988.
[11]	YING W, CHENG A C, WANG M S, et al. Comparative genomic analysis of duck enteritis virus strains[J]. J Virol, 2012, 86(24):13841-13842.
[12]	TAI S H S, NIIKURA M, CHENG H H, et al. Complete genomic sequence and an infectious BAC clone of feline herpesvirus-1 (FHV-1)[J]. Virology, 2010, 401(2):215-227.
[13]	DAVISON A J, SCOTT J E. The complete DNA sequence of varicella-zoster virus[J]. J Gen Virol, 1986, 67(Pt 9):1759-1816.
[14]	TAL-SINGER R, PENG C, PONCE DE LEON M, et al. Interaction of herpes simplex virus glycoprotein gC with mammalian cell surface molecules[J]. J Virol, 1995, 69(7):4471-4483.
[15]	SEDLACKOVA L, PERKINS K D, MEYER J, et al. Identification of an ICP27-responsive element in the coding region of a herpes simplex virus type 1 late gene[J]. J Virol, 2010, 84(6):2707-2718.
[16]	SARRAZIN S, LAMANNA W C, ESKO J D. Heparan sulfate proteoglycans[J]. Cold Spring Harb Perspect Biol, 2011, 3(7):a004952.
[17]	HEROLD B C, VISALLI R J, SUSMARSKI N, et al. Glycoprotein C-independent binding of herpes simplex virus to cells requires cell surface heparan sulphate and glycoprotein B[J]. J Gen Viroly1994, 75(Pt 6):1211-1222.
[18]	LEMBO D, DONALISIO M, LAINE C, et al. Auto-associative heparin nanoassemblies:a biomimetic platform against the heparan sulfate-dependent viruses HSV-1, HSV-2, HPV-16 and RSV[J]. Eur J Pharmaceut Biopharmaceut, 2014, 88(1):275-282.
[19]	IMAMURA J, SUZUKI Y, GONDA K, et al. Single particle tracking confirms that multivalent Tat protein transduction domain-induced heparan sulfate proteoglycan cross-linkage activates Rac1 for internalization[J]. J Biol Chem, 2011, 286(12):10581-10592.
[20]	SHUKLA D, SPEAR P G. Herpesviruses and heparan sulfate:an intimate relationship in aid of viral entry[J]. J Clin Invest, 2001, 108(4):503-510.
[21]	WIRTZ L, MÖCKEL M, KNEBEL-MÖRSDORF D. Invasion of herpes simplex Virus 1 into murine dermis:role of Nectin-1 and herpesvirus entry mediator as cellular receptors during aging[J]. J Virol, 2020, 94(5):e02046-19.
[22]	MONTGOMERY R I, WARNER M S, LUM B J, et al. Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF/NGF receptor family[J]. Cell, 1996, 87(3):427-436.
[23]	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.
[24]	HEROLD B C, WUDUNN D, SOLTYS N, et al. Glycoprotein C of herpes simplex virus type 1 plays a principal role in the adsorption of virus to cells and in infectivity[J]. J Virol, 1991, 65(3):1090-1098.
[25]	AZAB W, TSUJIMURA K, MAEDA K, et al. Glycoprotein C of equine herpesvirus 4 plays a role in viral binding to cell surface heparan sulfate[J]. Virus Res, 2010, 151(1):1-9.
[26]	RUE C A, RYAN P. A role for glycoprotein C in pseudorabies virus entry that is independent of virus attachment to heparan sulfate and which involves the actin cytoskeleton[J]. Virology, 2003, 307(1):12-21.
[27]	HU Y, LIU X K, ZOU Z, et al. Glycoprotein C plays a role in the adsorption of duck enteritis virus to chicken embryo fibroblasts cells and in infectivity[J]. Virus Res, 2013, 174(1-2):1-7.
[28]	KINGSLEY D H, KEELER C L JR. Infectious laryngotracheitis virus, an alpha herpesvirus that does not interact with cell surface heparan sulfate[J]. Virology, 1999, 256(2):213-219.
[29]	MÅRDBERG K, NYSTRÖM K, TARP M A, et al. Basic amino acids as modulators of an O-linked glycosylation signal of the herpes simplex virus type 1 glycoprotein gC:functional roles in viral infectivity[J]. Glycobiology, 2004, 14(7):571-581.
[30]	RUX A H, MOORE W T, LAMBRIS J D, et al. Disulfide bond structure determination and biochemical analysis of glycoprotein C from herpes simplex virus[J]. J Virol, 1996, 70(8):5455-5465.
[31]	MåRDBERG K, TRYBALA E, GLORIOSO J C, et al. Mutational analysis of the major heparan sulfate-binding domain of herpes simplex virus type 1 glycoprotein C[J]. J Gen Virol, 2001, 82(8):1941-1950.
[32]	FLYNN S J, RYAN P. The receptor-binding domain of pseudorabies virus glycoprotein gC is composed of multiple discrete units that are functionally redundant[J]. J Virol, 1996, 70(3):1355-1364.
[33]	JENTOFT N. Why are proteins O-glycosylated?[J]. Trends Biochem Sci, 1990, 15(8):291-294.
[34]	DELGUSTE M, PEERBOOM N, LE BRUN G, et al. Regulatory mechanisms of the mucin-like region on herpes simplex virus during cellular attachment[J]. ACS Chem Biol, 2019, 14(3):534-542.
[35]	NICOLA A V, HOU J, MAJOR E O, et al. Herpes simplex virus type 1 enters human epidermal keratinocytes, but not neurons, via a pH-dependent endocytic pathway[J]. J Virol, 2005, 79(12):7609-7616.
[36]	NICOLA A V, MCEVOY A M, STRAUS S E. Roles for endocytosis and low pH in herpes simplex virus entry into HeLa and Chinese hamster ovary cells[J]. J Virol, 2003, 77(9):5324-5332.
[37]	SARI T K, GIANOPULOS K A, WEED D J, et al. Herpes simplex virus glycoprotein C regulates Low-pH entry[J]. mSphere, 2020, 5(1):e00826-19.
[38]	WEED D J, DOLLERY S J, KOMALA SARI T, et al. Acidic pH mediates changes in antigenic and oligomeric conformation of herpes simplex virus gB and is a determinant of cell-specific entry[J]. J Virol, 2018, 92(17):e01034-18.
[39]	WEED D J, PRITCHARD S M, GONZALEZ F, et al. Mildly acidic pH triggers an irreversible conformational change in the fusion domain of herpes simplex virus 1 glycoprotein B and inactivation of viral entry[J]. J Virol, 2017, 91(5):e02123-16.
[40]	DOLLERY S J, DELBOY M G, NICOLA A V. Low pH-induced conformational change in herpes simplex virus glycoprotein B[J]. J Virol, 2010, 84(8):3759-3766.
[41]	JAROSINSKI K W, MARGULIS N G, KAMIL J P, et al. Horizontal transmission of Marek's disease virus requires US2, the UL13 protein kinase, and gC[J]. J Virol, 2007, 81(19):10575-10587.
[42]	JAROSINSKI K W, OSTERRIEDER N. Further analysis of Marek's disease virus horizontal transmission confirms that UL44 (gC) and UL13 protein kinase activity are essential, while US2 is nonessential[J]. J Virol, 2010, 84(15):7911-7916.
[43]	CHUARD A, COURVOISIER-GUYADER K, RÉMY S, et al. The tegument protein pUL47 of Marek's disease virus is necessary for horizontal transmission and is important for expression of glycoprotein gC[J]. J Virol, 2020, 95(2):e01645-20.
[44]	JAROSINSKI K W, OSTERRIEDER N. Marek's disease virus expresses multiple UL44 (gC) variants through mRNA splicing that are all required for efficient horizontal transmission[J]. J Virol, 2012, 86(15):7896-7906.
[45]	HARDY W R, SANDRI-GOLDIN R M. Herpes simplex virus inhibits host cell splicing, and regulatory protein ICP27 is required for this effect[J]. J Virol, 1994, 68(12):7790-7799.
[46]	PONNURAJ N, TIEN Y T, VEGA-RODRIGUEZ W, et al. The herpesviridae conserved multifunctional infected-cell protein 27 (ICP27) is important but not required for replication and oncogenicity of Marek's disease alphaherpesvirus[J]. J Virol, 2019, 93(4):e01903-18.
[47]	VEGA-RODRIGUEZ W, XU H, PONNURAJ N, et al. The requirement of glycoprotein C (gC) for interindividual spread is a conserved function of gC for avian herpesviruses[J]. Sci Rep, 2021, 11(1):7753.
[48]	VEGA-RODRIGUEZ W, PONNURAJ N, GARCIA M, et al. The requirement of glycoprotein c for interindividual spread is functionally conserved within the alphaherpesvirus genus (Mardivirus), but Not the Host (Gallid)[J]. Viruses, 2021, 13(8):1419.
[49]	LUBINSKI J M, WANG L Y, SOULIKA A M, et al. Herpes simplex virus type 1 glycoprotein gC mediates immune evasion in vivo[J]. J Virol, 1998, 72(10):8257-8263.
[50]	FRIEDMAN H M, COHEN G H, EISENBERG R J, et al. Glycoprotein C of herpes simplex virus 1 acts as a receptor for the C3b complement component on infected cells[J]. Nature, 1984, 309(5969):633-635.
[51]	HARRISON R A. The properdin pathway:an "alternative activation pathway" or a "critical amplification loop" for C3 and C5 activation?[J]. Semin Immunopathol, 2018, 40(1):15-35.
[52]	NILSSON B, EKDAHL K N. The tick-over theory revisited:is C3 a contact-activated protein?[J]. Immunobiology, 2012, 217(11):1106-1110.
[53]	MERLE N S, CHURCH S E, FREMEAUX-BACCHI V, et al. Complement system Part I-molecular mechanisms of activation and regulation[J]. Front Immunol, 2015, 6:262.
[54]	ARBORE G, KEMPER C, KOLEV M. Intracellular complement-the complosome-in immune cell regulation[J]. Mol Immunol, 2017, 89:2-9.
[55]	RICKLIN D, REIS E S, LAMBRIS J D. Complement in disease:a defence system turning offensive[J]. Nat Rev Nephrol, 2016, 12(7):383-401.
[56]	DEMPSEY P W, ALLISON M E, AKKARAJU S, et al. C3 d of complement as a molecular adjuvant:bridging innate and acquired immunity[J]. Science, 1996, 271(5247):348-350.
[57]	MAYILYAN K R. Complement genetics, deficiencies, and disease associations[J]. Protein Cell, 2012, 3(7):487-496.
[58]	FRIES L F, FRIEDMAN H M, COHEN G H, et al. Glycoprotein C of Herpes simplex virus 1 is an inhibitor of the complement cascade[J]. J Immunol, 1986, 137(5):1636-1641.
[59]	KOSTAVASILI I, SAHU A, FRIEDMAN H M, et al. Mechanism of complement inactivation by glycoprotein C of herpes simplex virus[J]. J Immunol, 1997, 158(4):1763-1771.
[60]	FRIEDMAN H M, WANG L, FISHMAN N O, et al. Immune evasion properties of herpes simplex virus type 1 glycoprotein gC[J]. J Virol, 1996, 70(7):4253-4260.
[61]	LUBINSKI J, WANG L Y, MASTELLOS D, et al. In vivo role of complement-interacting domains of herpes simplex virus type 1 glycoprotein gC[J]. J Exp Med, 1999, 190(11):1637-1646.
[62]	TAL-SINGER R, SEIDEL-DUGAN C, FRIES L, et al. Herpes simplex virus glycoprotein C is a receptor for complement component iC3b[J]. J Infect Dis, 1991, 164(4):750-753.
[63]	HUEMER H P, LARCHER C, COE N E. Pseudorabies virus glycoprotein III derived from virions and infected cells binds to the third component of complement[J]. Virus Res, 1992, 23(3):271-280.
[64]	HUEMER H P, NOWOTNY N, CRABB B S, et al. gp13 (EHV-gC):a complement receptor induced by equine herpesviruses[J]. Virus Res, 1995, 37(2):113-126.
[65]	HUNG S L, PENG C R L N, KOSTAVASILI I, et al. The interaction of glycoprotein C of herpes simplex virus types 1 and 2 with the alternative complement pathway[J]. Virology, 1994, 203(2):299-312.
[66]	AWASTHI S, BALLIET J W, FLYNN J A, et al. Protection provided by a herpes simplex virus 2 (HSV-2) glycoprotein C and D subunit antigen vaccine against genital HSV-2 infection in HSV-1-seropositive guinea pigs[J]. J Virol, 2014, 88(4):2000-2010.
[67]	AWASTHI S, MAHAIRAS G G, SHAW C E, et al. A dual-modality herpes simplex virus 2 vaccine for preventing genital herpes by using glycoprotein C and D subunit antigens to induce potent antibody responses and adenovirus vectors containing capsid and tegument proteins as T Cell immunogens[J]. J Virol, 2015, 89(16):8497-8509.
[68]	AWASTHI S, HOOK L M, SHAW C E, et al. A trivalent subunit antigen glycoprotein vaccine as immunotherapy for genital herpes in the guinea pig genital infection model[J]. Hum Vacc Immun, 2017, 13(12):2785-2793.
[69]	AWASTHI S, HOOK L M, PARDI N, et al. Nucleoside-modified mRNA encoding HSV-2 glycoproteins C, D, and E prevents clinical and subclinical genital herpes[J]. Sci Immunol, 2019, 4(39):eaaw7083.
[70]	EGAN K, HOOK L M, NAUGHTON A, et al. Herpes simplex virus type 2 trivalent protein vaccine containing glycoproteins C, D and E protects guinea pigs against HSV-1 genital infection[J]. Hum Vacc Immun, 2020, 16(9):2109-2113.
[71]	LUBINSKI J M, LAZEAR H M, AWASTHI S, et al. The herpes simplex virus 1 IgG fc receptor blocks antibody-mediated complement activation and antibody-dependent cellular cytotoxicity in vivo[J]. J Virol, 2011, 85(7):3239-3249.
[72]	SARI T K, GIANOPULOS K A, NICOLA A V. Glycoprotein C of herpes simplex Virus 1 shields glycoprotein B from antibody neutralization[J]. J Virol, 2020, 94(5):e01852-19.
[73]	HELDWEIN E E, LOU H, BENDER F C, et al. Crystal structure of glycoprotein B from herpes simplex virus 1[J]. Science, 2006, 313(5784):217-220.
[74]	COOPER R S, HELDWEIN E E. Herpesvirus gB:a finely tuned fusion machine[J]. Viruses, 2015, 7(12):6552-6569.
[75]	AWASTHI S, LUBINSKI J M, FRIEDMAN H M. Immunization with HSV-1 glycoprotein C prevents immune evasion from complement and enhances the efficacy of an HSV-1 glycoprotein D subunit vaccine[J]. Vaccine, 2009, 27(49):6845-6853.
[76]	AWASTHI S, LUBINSKI J M, SHAW C E, et al. Immunization with a vaccine combining herpes simplex virus 2 (HSV-2) glycoprotein C (gC) and gD subunits improves the protection of dorsal root ganglia in mice and reduces the frequency of recurrent vaginal shedding of HSV-2 DNA in guinea pigs compared to immunization with gD alone[J]. J Virol, 2011, 85(20):10472-10486.
[77]	HOOK L M, HUANG J L, JIANG M, et al. Blocking antibody access to neutralizing domains on glycoproteins involved in entry as a novel mechanism of immune evasion by herpes simplex virus type 1 glycoproteins C and E[J]. J Virol, 2008, 82(14):6935-6941.
[78]	METTENLEITER T C, ZSAK L, ZUCKERMANN F, et al. Interaction of glycoprotein gIII with a cellular heparinlike substance mediates adsorption of pseudorabies virus[J]. J Virol, 1990, 64(1):278-286.
[79]	OKAZAKI K, MATSUZAKI T, SUGAHARA Y, et al. BHV-1 adsorption is mediated by the interaction of glycoprotein gIII with heparinlike moiety on the cell surface[J]. Virology, 1991, 181(2):666-670.
[80]	OSTERRIEDER N. Construction and characterization of an equine herpesvirus 1 glycoprotein C negative mutant[J]. Virus Res, 1999, 59(2):165-177.
[81]	MAEDA K, HAYASHI S, TANIOKA Y, et al. Pseudorabies virus (PRV) is protected from complement attack by cellular factors and glycoprotein C (gC)[J]. Virus Res, 2002, 84(1-2):79-87.
[82]	HIDAKA Y, SAKAI Y, TOH Y, et al. Glycoprotein C of herpes simplex virus type 1 is essential for the virus to evade antibody-independent complement-mediated virus inactivation and lysis of virus-infected cells[J]. J Gen Virol, 1991, 72(Pt 4):915-921.
[83]	MACLEOD D T, NAKATSUJI T, YAMASAKI K, et al. HSV-1 exploits the innate immune scavenger receptor MARCO to enhance epithelial adsorption and infection[J]. Nat Commun, 2013, 4:1963.
[84]	GONZÁLEZ-MOTOS V, JVRGENS C, RITTER B, et al. Varicella zoster virus glycoprotein C increases chemokine-mediated leukocyte migration[J]. PLoS Pathog, 2017, 13(5):e1006346.
[85]	MAEDA K, HORIMOTO T, MIKAMI T. Properties and functions of feline herpesvirus type 1 glycoproteins[J]. J Vet Med Sci, 1998, 60(8):881-888.
[86]	TRYBALA E, SVENNERHOLM B, BERGSTRÖM T, et al. Herpes simplex virus type 1-induced hemagglutination:glycoprotein C mediates virus binding to erythrocyte surface heparan sulfate[J]. J Virol, 1993, 67(3):1278-1285.
[87]	OKAZAKI K, KANNO T, KIRIYA S, et al. Hemadsorptive activity of transfected COS-7 cells expressing BHV-1 glycoprotein gIII[J]. Virology, 1993, 193(2):1024-1027.
[88]	YAMADA S, IMADA T, SHIMIZU M, et al. A mutant of pseudorabies virus with deletion of glycoprotein gIII gene prepared from a Japanese isolate:it fails to agglutinate mouse erythrocytes[J]. Vet Microbiol, 1995, 45(2-3):233-242.
[89]	ANDOH K, HATTORI S, MAHMOUD H Y A H, et al. The haemagglutination activity of equine herpesvirus type 1 glycoprotein C[J]. Virus Res, 2015, 195:172-176.