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人巨细胞病毒(HCMV)感染在人群中极其普遍,病毒一旦侵入机体,将长期存在于体内,且具有潜伏-活化的生物学特性。在病毒与宿主共同进化的漫长过程中,病毒靶向性的产生了多种免疫逃避机制,通过编码病毒自身免疫调节分子,参与调控机体主要组织相容性复合体、细胞免疫、体液免疫、细胞因子及趋化因子等方面的功能,以躲避宿主的免疫杀伤作用。HCMV的免疫调节基因被认为在病毒的致病机制中扮演重要角色。本文将对近年来有关HCMV的免疫调控机制研究作一综述,从病毒编码的免疫调节分子功能的角度并结合本实验室的相关研究成果,探讨病毒与宿主免疫的相互作用过程,从病毒干预宿主免疫关键分子作用的角度映射机体对抗病毒的免疫机理。
Abstract：Human cytomegalovirus(HCMV) is an ubiquitous pathogen that infects a majority of the world′s population.The virus can establish lifelong infection once the human body is infected by HCMV and virus can be reactivated from a latent state in immune suppressed individuals.HCMV has developed several strategies to evade host immune surveillance after millions of years of co-evolution with mankind.One of the classical tricks is encoding homologous to human immune factors or stealing host cellular genes that have significant functions in immune system.Virus encoded immune modulators which participate in regulating the major histocompatibility complex,cellular immunity,humoral immunity,cytokines and chemokines are supposed to play a significant role in the pathogenesis of HCMV.Evaluation of "mutually assured survival" relationship between virus and host provides important insights into viral immunopathogenesis and study of viral immunomodulatory proteins might help us to uncover new human genes that control immunity.
[1]Brit W J,Alford C A.Cytomegalovirus.In FieldsVirology[J].1996,2(3):2493-2523.
[2]Oresic K,Tortorella D.ER chaperones participate inHCMV US2-mediated degradation of class I MHC mol-ecules[J].J Gen Virol,2008,89(5):1122-1130.
[3]Hegde N R,Tomazin R A,Wisner T W,et al.Inhibi-tion of HLA-DR assembly,transport,and loading byHuman Cytomegalovirus glycoprotein US3:a novelmechanism for evading major histocompatibility com-plex class II antigen presentation[J].J Virol,2002,76(21):10929-10941.
[4]Halenius A,Hauka S,Dlken L,et al.Peptide-Loadingcomplex and inhibits histocompatibility complex class Ihuman cytomegalovirus disrupts the major tapasin genetranscription[J].J Virol,2011,85(7):3473-3485.
[5]Lee S O,Hwang S,Park J,et al.Functional dissectionof HCMV US11in mediating the degradation of MHCclass I molecules[J].Biochem Bioph Res Co,2005,330(4):1262-1267.
[6]Noriega V M,Tortorella D.Human cytomegalovirus-encoded immune modulators partner to downregulatemajor histocompatibility complex class I molecules[J].J Virol,2009,83(3):1359-1367.
[7]Wang E C,McSharry B,Retiere C,et al.UL40-media-ted NK evasion during productive infection with humancytomegalovirus[J].PNAS,2002,99(11):7570-7575.
[8]Wilkinsona G W,Tomaseca P,Stantona R J,et al.Modulation of natural killer cells by human cytomegalo-virus[J].J Clin Virol,2008,41(3):206-212.
[9]Müller S,Zocher G,Steinle A,et al.Structure of theHCMV UL16-MICB complex elucidates select bindingof a viral immunoevasin to diverse NKG2Dligands[J].PLoS Pathog,2010,6(1):1-12.
[10]Wills M R,Ashiru O,Reeves M B,et al.Human cyto-megalovirus encodes an MHC class I-like molecule(UL142)that functions to inhibit NK cell lysis[J].JImmunol,2005,175(11):7457-7465.
[11]Prodhomme V,Sugrue D M,Stanton R J,et al.Hu-man cytomegalovirus UL141promotes efficient down-regulation of the natural killer cell activating ligandCD112[J].J Gen Virol,2010,91(8):2034-2039.
[12]Stern-Ginossar N,Elefant N,Zimmermann A,et al.Host immune system gene targeting by a viral miRNA[J].Science,2007,317:376-381.
[13]Furukawa T,Hornberger E,Sarkuma S,et al.Dem-onstration of immunoglobulin G receptors induced byhuman cytomegalovirus[J].J Clin Microbiol,1975,2:332-336.
[14]Sakuma S,Furukawa T,Plotkin S A.The character-ization of IgG receptor induced by human cytomegalov-irus[J].Proc Soc Exp Biol Med,1977,155:168-172.
[15]Maccormac L P,Grundy J E.Human cytomegalovirusinduces an Fc gamma receptor(Fc gammaR)in endo-thelial cells and fibroblasts that is distinct from the hu-man cellular Fc gammaRs[J].J Infect Dis,1996,174:1151-1161.
[16]Xu B,Murayama T,Ishida K,et al.Characterizationof IgG Fc receptors induced by human cytomegalovirus[J].J Gen Virol,1989,70(4):893-900.
[17]Rahman A A,Teschner M,Sethi K K,et al.Appear-ance of IgG Fc receptors on cultured human fibroblastsinfected with human cytomegalovirus[J].J Immunol,1976,117:253-258.
[18]Lilley B N,Ploegh H L,Tirabassi R S.Human cyto-megalovirus open reading frame TRL11/IRL11encodesan immunoglobulin G Fc-binding protein[J].J Virol,2001,75:1218-1221.
[19]Atalay R,Zimmermann A,Wagner M,et al.Identifi-cation and expression of human cytomegalovirus tran-scription units coding for two distinct Fc gamma recep-tor homologs[J].J Virol,2002,76:8596-8608.
[20]Spiller O B,Morgan B P,Tufaro F,et al.Altered ex-pression of host encoded complement regulators on hu-man cytomegalovirus infected cells[J].Eur J Immunol,1996,26:1532-1538.
[21]Spiller O B,Hanna S M,Devine D V,et al.Neutral-ization of cytomegalovirus virions:the role of comple-ment[J].J Infect Dis,1997,176:339-347.
[22]Spear G T,Lurain N S,Parker C J,et al.Host cell-derived complement control proteins CD55and CD59are incorporated into the virions of two unrelated enve-loped viruses[J].J Immunol,1995,155:4376-4381.
[23]Rahbar A,Bostrm L,Sderberg-Naucler C.Detec-tion of cytotoxic CD13-specific autoantibodies in serafrom patients with ulcerative colitis and Crohn's disease[J].J Autoimmun,2006,26(3):155-164.
[24]Kotenko S V,Saccani S,Izotova L S,et al.Humancytomegalovirus harbors its own unique IL-10homolog(cmvIL-10)[J].Proc Natl Acad Sci USA,2000,97:1695-1700.
[25]Spencer J V.Potent immunosuppressive activities ofcytomegalovirus-encoded interleukin-10[J].J Virol,2002,76:1285-1292.
[26]Benedict C A.Cutting edge:a novel viral TNF recep-tor superfamily member in virulent strains of humancytomegalovirus[J].J Immunol,1999,162:6967-6970.
[27]Ryckman B J,Rainish B L,Chase M C,et al.Charac-terization of the human cytomegalovirus gH/gL/UL128-131complex that mediates entry into epithelialand endothelial cells[J].J Virol,2008,82(1):60-70.
[28]Ritter T,Brandt C,Prsch S,et al.Stimulatory andinhibitory action of cytokines on the regulation of hC-MV-IE promoter activity in human endothelial cells[J].Cytokine,2000,12(8):1163-1170.
[29]Paulus C,Krauss S,Nevels M.A human cytomegalo-virus antagonist of type I IFN-dependent signal trans-ducer and activator of transcription signaling[J].ProcNatl Acad Sci USA,2006,103:3840-3845.
[30]Huh Y H,Kim Y E,Park J J,et al.Binding STAT2by the acidic domain of human cytomegalovirus IE1promotes viral growth and is negatively regulated bySUMO[J].J Virol,2008,82:10444-10454.
[31]Browne E P,Wing B,Coleman D,et al.Altered cellu-lar mRNA levels in human cytomegalovirus-infectedfibroblasts:viral block to the accumulation of antiviralmRNA[J].J Virol,2001,75:12319-12330.
[32]Child S J,Harson L K,Brown C E,et al.Double-stranded RNA binding by a heterodimeric complex ofmurine cytomegalovirus m142and m143proteins[J].JVirol,2006,80:10173-10180.
[33]Hakki M,Geballe A P.Double-stranded RNA bindingby human cytomegalovirus pTRSI[J].J Virol,2007,9:7311-7318.
[34]Hakki M,Marshall E E,De Niro K L,et al.Bindingand nuclear relocalization of protein kinase R by humancytomegalovirus TRSI[J].J Virol,2006,80:11817-11826.
[35]Lalani A S.The purified myxoma virusγ-interferon re-ceptor homolog M-T7interacts with the heparin-bind-ing domains of chemokines[J].J Virol,1997,71:4356-4363.
[36]Rollins B J.Chemokines[J].Blood,1997,90:909-928.
[37]Cinamon G,Shinder V,Alon R.Sheer forces promotelymphocyte migration across vascular endotheliumbearing apical chemokines[J].Nature Immunol,2001,2:515-522.
[38]Murphy P M.Viral exploitation and subversion of theimmune system through chemokine mimicry[J].Na-ture,2001,2(2):116-122.
[39]Saederup N,Mocarski E.Fatal attraction:cytomega-lovirus-encoded chemokine homologs[J].Curr Top Mi-crobiol Immunol,2002,269:235-256.
[40]Waldhoer M,Kledal T N,Farrell H,et al.HumanCMV US28receptors exhibit similar murine Cytomega-lovirus(CMV)M33and constitutive signaling activi-ties[J].J Virol,2002,76(16):8161-8168.
[41]Bodaghi B.Chemokine sequestration by viral chemore-ceptors as a novel viral escape strategy:withdrawal ofchemokines from the environment of cytomegalovirus-infected cells[J].J Exp Med,1998,188:855-866.
[42]Fraile-Ramos A,Kledal T N,Pelchen-Matthews A,etal.The human cytomegalovirus US28protein is locatedin endocytic vesicles and undergoes constitutive endocy-tosis and recycling[J].Mol Biol Cell,2001,12:1737-1749.
[43]Fraile-Ramos A,Pelchen-Matthews A,Kledal T N,etal.Localization of HCMV UL33and US27in endocyticcompartments and viral membranes[J].Traffic,2002,3:218-232.
[44]Zheng Q,Tao R,Gao H H,et al.HCMV-EncodedUL128enhances TNF-a and IL-6expression and pro-motes PBMC proliferation through the MAPK/ERKpathway in vitro[J].Viral Immunol,2012,25(2):1-8.
[45]Tripp R A,Jones L P,Haynes L M,et al.CX3Cchemokine mimicry by respiratory syncytial virus Gglycoprotein[J].Nature Immunol,2001,2:732-738.
[46]Locati M,Murphy P M.Chemokines and chemokinereceptors:biology and clinical relevance in inflamma-tion and AIDS[J].Annu Rev Med,1999,50:425-440.
[47]Wang D,Shenk T.Human cytomegalovirus virionprotein complex required for epithelial and endothelialcell tropism[J].Proc Natl Acad Sci USA,2005,102(50):18153-18158.
[48]Nichols W G,Corey L,Gooley T,et al.High risk ofdeath due to bacterial and fungal infection among cyto-megalovirus(CMV)-seronegative recipients of stemcell transplants from seropositive donors:evidence forindirect effects of primary CMV infection[J].J InfectDis,2002,185:273-282.
[49]George M J,Snydman D R,Werner B G,et al.Theindependent role of cytomegalovirus as a risk factor forinvasive fungal disease in orthotopic liver transplantrecipients[J].Am J Med 1997,103:106-113.
[50]Griffin D.Potential mechanisms of immune suppression[J].Viral Pathogenesis,1996,207-235.
[51]Rinaldo C J r,Garney W P,Richter B S,et al.Mecha-nisms of immunosuppression in cytomegaloviral mono-nucleosis[J].J Infect Dis,1980,141:488-495.
[52]Levin M J,Rinaldo C Jr,Leary P L,et al.Immuneresponse to herpesvirus antigens in adults with acutecytomegalovirus mononucleosis[J].J Infect Dis,1979,140:851-857.
[53]Stein J,Volk H D,Liebenthal C,et al.Tumor necrosisfactor alpha stimulates the activity of the human cyto-megalovirus major immediate early enhancer/promoterin immature monocytic cells[J].J Gen Virol,1993,74:2333-2338.
[54]Alcami A.Viral mimicry of cytokines,chemokines andtheir receptors[J].Nature Rev Immunol,2003,3(1):36-50.
[55]Miller-Kittrell M,Sparer T E.Feeling manipulated:cytomegalo-virus immune manipulation[J].Virol J,2009,6(4):1-20.
基本信息:
DOI：10.13242/j.cnki.bingduxuebao.002356
中图分类号:R373.9
引用信息:
[1]郑琪,陶然,尚世强.人巨细胞病毒博弈宿主免疫进展[J].病毒学报,2013,29(01):85-91.DOI:10.13242/j.cnki.bingduxuebao.002356.
2013-01-31
2013-01-31
2013-01-31