SARS-CoV Spike蛋白受体结合结构域在哺乳动物细胞中的表达、纯化及功能研究
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摘要
严重急性呼吸综合征(severe acute respiratory syndrome,SARS)是一种新出现的感染性疾病,其致病体为SARS-CoV。SARS能够导致严重急性肺损伤,许多病人恶化为急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS),具有很高的致死率。此外,受感染者的多个组织、器官受损。SARS具有较高的发病率、致死率,且传播速度快,严重影响了社会、经济的发展。
     研究表明,Spike(S)蛋白是SARS-CoV表面最重要的结构蛋白,能够介导病毒与宿主细胞受体的结合和膜融合。同时,它能够诱导宿主的免疫反应,产生中和抗体。因此,SARS-CoV S蛋白对于确定SARS-CoV的致病机理及疫苗研发非常重要。由于SARS-CoV的S蛋白本身的编码序列在哺乳动物细胞中的表达量极低,难以满足研究需要。为了解决这个问题,SARS-CoV的S蛋白本身的编码序列被替换为人类基因高频使用的密码子,S蛋白得到高量表达,获得了大量有生物活性的S蛋白。为SARS-CoV S蛋白介导的致病机理的进一步研究和SARS-CoV疫苗的研发提供了基础。
     SARS-CoV的受体结合结构域(receptor binding domain,RBD)定位于S蛋白的第319到510位氨基酸(AA319-510)。这段多肽能够介导病毒与其受体ACE2结合,决定了病毒的宿主范围和细胞向性。同时,它含有SARS-CoV主要的中和表位,能够诱导中和抗体。通过人类密码子优化的策略,我们获得了大量有生物活性的RBD S蛋白。SARS-CoV进入细胞由S蛋白介导。我们的研究表明,RBD S蛋白能单独通过病毒受体ACE2进入靶细胞。同时,RBD S蛋白N连接的糖基化的去除不能消除RBD S蛋白的这种功能。这些研究将为SARS-CoV感染的分子机制提供新的线索,同时对于靶向病毒进入的治疗性药物的发展提供重要的启示。
     本论文的最后一部分在哺乳动物细胞中表达了肌肉发育重要抑制因子myostatin。
Severe acute respiratory syndrome (SARS) is a new infectious disease caused by SARS coronavirus (SARS-CoV). The clinical presentation indicates that acute lung injury is the major clinical characteristic of SARS and leads to acute respiratory distress syndrome (ARDS) in some severe SARS patients, whose motality is very high. SARS can induce a system disease and impair many other organs apart from lung. Due to its high morbidity and mortality and widespread occurrence, SARS has profoundly disturbed social and economic development.
     SARS-CoV Spike (S) protein is the most important structural protein on the surface of the SARS-CoV, which forms morphologically characteristic projections on the virion surface, mediates binding to host receptors and membrane fusion. S protein is known to be responsible for inducing host immune responses and virus neutralization by antibodies. S protein is important for pathogenesis study and vaccine development of SARS-CoV. In mammalian cells, the expression level of SARS-CoV S protein encoded by native codons is very low, which is hard to meet the needs of research. To solve this problem, the native codons of SARS-CoV S protein were replaced by codons used frequently by human genes. A large amount of bioactive SARS-CoV S protein was obtained. It is a basement for the research on pathogenesis mediated by SARS-CoV S protein and the development of SARS-CoV vaccine.
     The receptor-binding domain (RBD) of SARS-CoV is mapped to the amino acids 319-510 on S protein, which can mediate the binding of virus and the virus receptor ACE2, and therefore determine the range of host and cell tropism. At the same time, it contains major neutralization epitopes and can induce neutralization antibody. By human codon-optimization, a large amount of bioactive RBD S protein was obtained. Cell entry of SARS-CoV is mediated by the viral S protein. We demonstrated that RBD S protein alone could enter SARS-CoV susceptible cells through the virus receptor ACE2. We also showed the removal of N-glycans of RBD S protein did not abolish this function. Our discoveries that the RBD S protein alone can enter the cells and the glycosylation of RBD spike protein has no effect on the virus entry provide additional elucidation on the molecular mechanism of SARS-CoV infection. These might be important implications for the development of therapeutic drugs targeted to virus entry.
     The last part of this thesis is the expression of an important inhibitor to muscle development, myostatin, in mammalian cells.
引文
1. Andre S, Seed B, Eberle J, Schraut W, Bultmann A, and Haas J. Increased immune response elicited by DNA vaccination with a synthetic gp120 sequence with optimized codon usage. J. Virol. 1998,72: 1497-1503.
    2. Bashirova AA, Geijtenbeek TB, van Duijnhoven GC, van Vliet SJ, Eilering JB, Martin MP, Wu L, Martin TD, Viebig N, Knolle PA, KewalRamani VN, van Kooyk Y, Carrington M. A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection. J Exp Med.2001, 193:671-678.
    3. Bisht H, Roberts A, Vogel L, Bukreyev A, Collins PL, Murphy BR, Subbarao K, Moss B. Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice.Proc Natl Acad Sci U S A. 2004, 101: 6641-6646.
    4. Bukreyev A, Lamirande EW, Buchholz UJ, Vogel LN, Elkins WR, St Claire M, Murphy BR, Subbarao K, Collins PL.Mucosal immunisation of African green monkeys (Cercopithecus aethiops) with an attenuated parainfluenza virus expressing the SARS coronavirus spike protein for the prevention of SARS. Lancet. 2004,363:2122-2127.
    5. Cantin C, Holguera J, Ferreira L, Villar E, Munoz-Barroso I. Newcastle disease virus may enter cells by caveolae-mediated endocytosis.J Gen Virol. 2007, 88: 559-569.
    6. Chakraborti S, Prabakaran P, Xiao X, Dimitrov DS. The SARS Coronavirus S Glycoprotein Receptor Binding Domain: Fine Mapping and Functional Characterization. Virol J. 2005, 2: 73-82.
    7. Chen Z, Zhang L, Qin C, Ba L, Yi CE, Zhang F, Wei Q, He T, Yu W, Yu J, Gao H, Tu X, Gettie A, Farzan M, Yuen KY, Ho DD. Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region. J Virol. 2005, 79: 2678-2688.
    8. De Groot AS. How the SARS vaccine effort can learn from HIV~speeding towards the future, learning from the past. Vaccine .2003, 21: 4095-4104.
    9. Ding Y, He L, Zhang Q, Huang Z, Che X, Hou J, Wang H, Shen H, Qiu L, Li Z, Geng J, Cai J, Han H, Li X, Kang W, Weng D, Liang P, Jiang S.Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J. Pathol. 2004, 203: 622-630.
    10. Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ. Res. 2000, 87: E1—9.
    11. Eickmann M, Becker S, Klenk HD, Doerr HW, Stadler K, Censini S, Guidotti S, Masignani V, Scarselli M, Mora M, Donati C, Han JH, Song HC, Abrignani S, Covacci A, Rappuoli R. Phylogeny of the SARS coronavirus.Science 2003, 302: 1504-1505.
    12. Fackler OT, Peterlin BM.Endocytic entry of HIV-1. Curr Biol. 2000, 10: 1005-1008.
    13. Fenouillet E, Gluckman JC, Bahraoui E. Role of N-linked glycans of envelope glycoproteins in infectivity of human immunodeficiency virus type 1. J. Virol. 1990, 64: 2841-2848.
    14. Greber UF. Signalling in viral entry. Cell. Mol. Life Sci. 2002, 59: 608-626.
    15. Haas J, Park EC, Seed B. Codon usage limitation in the expression of HIV-1 envelope glycoprotein. Curr Biol. 1996,6:315-324.
    16. Hamming I,Timens W, Bulthuis ML, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J. Pathol. 2004, 203: 631-637.
    17. Haun G, Keppler OT, Bock CT, Herrmann M, Zentgraf H, Pawlita M. The cell surface receptor is a major determinant restricting the host range of the B-lymphotropic papovavirus. J Virol. 1993, 67: 7482-7492.
    18. He Y, Lu H, Siddiqui P, Zhou Y, Jiang S. Receptor-binding domain of SARS coronavirus spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies. J Immunol. 2005, 174: 4908-4915.
    19. He Y, Zhou Y, Liu S, Kou Z, Li W, Farzan M, Jiang S. Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine. Biochem. Biophys. Res. Commun. 2004, 324: 773- 781.
    20. He Y, Zhou Y, Siddiqui P, Jiang S. Inactivated SARS-CoV vaccine elicits high titers of spike protein-specific antibodies that block receptor binding and virus entry. Biochem Biophys Res Commun. 2004, 325: 445-452.
    21. He Y, Zhu Q, Liu S, Zhou Y, Yang B, Li J, Jiang S. Identification of a critical neutralization determinant of severe acute respiratory syndrome (SARS)-associated coronavirus: importance for designing SARS vaccines. Virology 2005, 334: 74-82.
    22. Inoue Y, Tanaka N, Tanaka Y, Inoue S, Morita K, Zhuang M, Hattori T, Sugamura K. Clathrin-dependent entry of severe acute respiratory syndrome coronavirus into target cells expressing ACE2 with the cytoplasmic tail deleted. J Virol. 2007, 81: 8722-8729.
    23. Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, Huan Y, Yang P, Zhang Y, Deng W, Bao L, Zhang B, Liu G, Wang Z, Chappell M, Liu Y, Zheng D, Leibbrandt A, Wada T, Slutsky AS, Liu D, Qin C, Jiang C, Penninger JM. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005, 11: 875-879.
    24. Leung WK, To KF, Chan PK, Chan HL, Wu AK, Lee N, Yuen KY, Sung JJ. Enteric involvement of severe acute respiratory syndrome-associated coronavirus infection. Gastroenterology 2003, 125: 1011-1017.
    25. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003, 426: 450- 454.
    26. Li W, Zhang C, Sui J, Kuhn JH, Moore MJ, Luo S, Wong SK, Huang IC, Xu K, Vasilieva N, Murakami A, He Y, Marasco WA, Guan Y, Choe H, Farzan M.EMBO J. 2005, 24: 1634-1643.
    27. Marino, M. H. Expression systems for heterologous protein production. BioPharm. 1989, 2: 18-33.
    28. Marsh M, Helenius A. Virus entry: open sesame. Cell 2006, 124: 729-740.
    29. Moore JP, McKeating JA, Norton WA, Sattentau QJ. Direct measurement of soluble CD4 binding to human immunodeficiency virus type 1 virions: gp120 dissociation and its implications for virus-cell binding and fusion reactions and their neutralization by soluble CD4. J Virol. 1991, 65: 1133-1140.
    30. Nemerow GR. Cell receptors involved in adenovirus entry. Virology 2000, 274: 1-4.
    31. Paizis G, Tikellis C, Cooper ME, Schembri JM, Lew RA, Smith AI, Shaw T, Warner FJ, Zuilli A, Burrell LM, Angus PW. Chronic liver injury in rats and humans upregulates the novel enzyme angiotensin convertign enzyme 2. Gut, 2005, 54: 1790-1796.
    32. Pelkmans L, Helenius A. Insider information: what viruses tell us about endocytosis. Curr. Opin. Cell Biol. 2003, 15:414-422.
    33. Pelkmans L, Puntener D, Helenius A. Local actin polymerization and dynamin recruitment in SV40-induced internalization of caveolae. Science 2002, 296: 535-539.
    34. Rota PA, Oberste MS, Monroe SS, Nix WA, Campagnoli R, Icenogle JP, Pefiaranda S, Bankamp B, Maher K, Chen MH, Tong S, Tamin A, Lowe L, Frace M, DeRisi JL, Chen Q, Wang D, Erdman DD, Peret TC, Burns C, Ksiazek TG, Rollin PE, Sanchez A, Liffick S, Holloway B, Limor J, McCaustland K, Olsen-Rasmussen M, Fouchier R, Günther S, Osterhaus AD, Drosten C, Pallansch MA, Anderson LJ, Bellini WJ. Characterization of a novel coronavirus associated with severe acute respiratory syndrome, Science 2003, 300: 1394-1399.
    35. Scearce-Levie K, Lieberman MD, Elliott HH, Conklin BR. Engineered G protein coupled receptors reveal independentregulation of internalization, desensitization and acute signaling. 2005. BMC. Biol. 3, 3.
    36. Simmons G, Reeves JD, Rennekamp AJ, Amberg SM, Piefer AJ, Bates P. Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoproteinmediated viral entry.Proc. Natl. Acad. Sci. U.S.A.2004, 101: 4240-4245.
    37. Soilleux EJ, Barten R, Trowsdale J. DC-SIGN; a related gene, DC-SIGNR; and CD23 form a cluster on 19p13. J. Immunol.2000, 165: 2937-2942.
    38. Soilleux EJ. DC-SIGN (dendritic cell-specific ICAM-grabbing nonintegrin) and DC-SIGN-related (DC-SIGNR): friend or foe? Clin. Sci. 2003, 104: 437-446.
    39. Song HD, Tu CC, Zhang GW, Wang SY, Zheng K, Lei LC, Chen QX, Gao YW, Zhou HQ, Xiang H, Zheng HJ, Chern SW, Cheng F, Pan CM, Xuan H, Chen SJ, Luo HM, Zhou DH, Liu YF, He JF, Qin PZ, Li LH, Ren YQ, Liang WJ, Yu YD, Anderson L, Wang M, Xu RH, Wu XW, Zheng HY, Chen JD, Liang G, Gao Y, Liao M, Fang L, Jiang LY, Li H, Chen F, Di B, He LJ, Lin JY, Tong S, Kong X, Du L, Hao P, Tang H, Bernini A, Yu XJ, Spiga O, Guo ZM, Pan HY, He WZ, Manuguerra JC, Fontanet A, Danchin A, Niccolai N, Li YX, Wu CI, Zhao GP.Proc. Natl. Acad. Sci. U.S.A.2005, 102: 2430-2435.
    40. Stadler K, Masignani V, Eickmann M, Becker S, Abrignani S, Klenk HD, Rappuoli R. SARS-beginning to understand a new virus. Nat Rev Microbiol. 2003, 1: 209-218.
    41. Sui J, Li W, Murakami A, Tamin A, Matthews LJ, SWong K, Moore MJ, Tallarico AS, Olurinde M, Choe H, Anderson LJ, Bellini WJ, Farzan M, Marasco WA. Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association. Proc. Natl. Acad. Sci. U.S.A. 2004, 101: 2536-2541.
    42. Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003 , 21 April 2004, world health organization,(http://www.who.int/csr/sars/country/table2004_04_21 /en/index.html) .
    43. Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ.A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J. Biol. Chem. 2000, 275: 33238-33243.
    44. van den Brink EN, Ter Meulen J, Cox F, Jongeneelen MA, Thijsse A, Throsby M, Marissen WE, Rood PM, Bakker AB, Gelderblom HR, Martina BE, Osterhaus AD, Preiser W, Doerr HW, de Kruif J, Goudsmit J. Molecular and biological characterization of human monoclonal antibodies binding to the spike and nucleocapsid proteins of severe acute respiratory syndrome coronavirus. J Virol. 2005, 79: 1635-1644.
    45. Wang D, Lu J. Glycan arrays lead to the discovery of autoimmunogenic activity of SARS-CoV. Physiol Genomics. 2004, 18: 245-248.
    46. Wang HL, Yang P, Liu KT, Guo F, Zhang YL, Zhang GY , Jiang CY. SARS coronavirus can enter cells in a non-clathrin dependent non-caveolae dependent endocytic pathway. Cell research (Accepted)
    47. Wang S, Chou TH, Sakhatskyy PV, Huang S, Lawrence JM, Cao H, Huang X, Lu S.Identification of two neutralizing regions on the severe acute respiratory syndrome coronavirus spike glycoprotein produced from the mammalian expression system. J Virol. 2005, 79: 1906-1910.
    48. Wang YD, Sin WY, Xu GB, Yang HH, Wong TY, Pang XW, He XY, Zhang HG, Ng JN, Cheng CS, Yu J, Meng L, Yang RF, Lai ST, Guo ZH, Xie Y, Chen WF. T-cell epitopes in severe acute respiratory syndrome (SARS) coronavirus spike protein elicit a specific T-cell immune response in patients who recover from SARS. J. Virol. 2004, 78: 5612-5618.
    49. Warner FJ, Smith AI, Hooper NM, Turner AJ. Angiotensin-converting enzyme-2: a molecular and cellular perspective. Cell Mol Life Sci. 2004, 61: 2704-2713.
    50. Wong SK, Li W, Moore MJ, Choe H, Farzan M. A 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2. J. Biol. Chem. 2004, 279: 3197-3201.
    51. Wurm FM, Production of recombinant protein therapeutics in cultivated mammalian cells, Nat. Biotechnol. 2004, 22: 1393 - 1398.
    52. Yang ZY, Huang Y, Ganesh L, Leung K, Kong WP, Schwartz O, Subbarao K, Nabel GJ. pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN. J Virol. 2004, 78: 5642-5650.
    53. Yang ZY, Kong WP, Huang Y, Roberts A, Murphy BR, Subbarao K, Nabel GJ.A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature 2004, 428: 561-564.
    1. Argiles JM, Almendro V, Busquets S, Lopez-Soriano FJ. The pharmacological treatment of cachexia. Curr Drug Targets. 2004, 5: 265-277.
    2. Joulia D, Bernardi H, Garandel V, Rabenoelina F, Vernus B, Cabello G. Mechanisms involved in the inhibition of myoblast proliferation and differentiation by myostatin.Exp Cell Res. 2003, 286: 263-275.
    3. Langley B, Thomas M, Bishop A, Sharma M, Gilmour S, Kambadur R. Myostatin inhibits myoblast differentiation by down-regulating MyoD expression. J Biol Chem. 2002, 277: 49831-49840.
    4. Lee SJ, McPherron AC. Regulation of myostatin activity and muscle growth. Proc Natl Acad Sci U SA. 2001, 98: 9306-9311.
    5. Lin J, Arnold HB, Della-Fera MA, Azain MJ, Hartzell DL, Baile CA. Myostatin knockout in mice increases myogenesis and decreases adipogenesis. Biochem Biophys Res Commun 2002, 291: 701-706.
    6. McPherron AC, Lawler AM, Lee SM. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 1997, 387: 83-90.
    7. McPherron AC, Lee SJ. Suppression of body fat accumulation in myostatin-deficient mice. J Clin Invest. 2002, 109:595-601.
    8. Philip B, Lu Z, Gao Y. Regulation of GDF-8 signaling by the p38 MAPK._Cell Signal. 2005, 17: 365-375.
    9. Rebbapragada A, Benchabane H, Wrana JL, Celeste AJ, Attisano L. Myostatin signals through a transforming growth factor beta-like signaling pathway to block adipogenesis.Mol Cell Biol. 2003, 23: 7230-7242.
    10. Ríos R, Carneiro I, Arce VM, Devesa J. Myostatin regulates cell survival during C2C12 myogenesis._Biochem Biophys Res Commun. 2001, 280: 561-566.
    11. Rios R, Fernandez-Nocelos S, Carneiro 1, Arce VM and Devesa J. Differential response to exogenous and endogenous myostatin in myoblasts suggests that myostatin acts as an autocrine factor in vivo. Endocrinology 2004, 145: 2795-2803.
    12. Scott IC, Blitz IL, Pappano WN, Imamura Y, Clark TG, Steiglitz BM, Thomas CL, Maas SA, Takahara K, Cho KW, Greenspan DS. Mammalian BMP-1/Tolloid-related metalloproteinases, including novel family member mammalian Tolloid-like 2, have differential enzymatic activities and distributions of expression relevant to patterning and skeletogenesis. Dev Biol. 1999, 213: 283-300.
    13. Taylor WE, Bhasin S, Artaza J, Byhower F, Azam M, Willard DH Jr, Kull FC Jr, Gonzalez-Cadavid N. Myostatin inhibits cell proliferation and protein synthesis in C2C12 muscle cells. Am J Physiol Endocrinol Metab. 2001, 280: E221-228.
    14. Thomas M, Langley B, Berry C, Sharma M, Kirk S, Bass J, Kambadur R. Myostatin, a negative regulator of muscle growth, functions by inhibiting myoblast proliferation.J Biol Chem. 2000, 275: 40235-40243.
    15. Tobin JF, Celeste AJ. Myostatin, a negative regulator of muscle mass: implications for muscle degenerative diseases. Curr Opin Pharmacol. 2005 Jun;5(3):328-32.
    16. Tobin JF, Celeste AJ. Myostatin, a negative regulator of muscle mass: implications for muscle degenerative diseases. Curr Opin Pharmacol. 2005, 5: 328-332.
    17. Walsh FS, Celeste AJ. Myostatin: a modulator of skeletal-muscle stem cells. Biochem Soc Trans. 2005,33: 1513-1517.
    18. Whittemore LA, Song K, Li X, Aghajanian J, Davies M, Girgenrath S, Hill JJ, Jalenak M, Kelley P, Knight A, Maylor R, O'Hara D, Pearson A, Quazi A, Ryerson S, Tan XY, Tomkinson KN, Veldman GM, Widom A, Wright JF, Wudyka S, Zhao L, Wolfman NM. Inhibition of myostatin in adult mice increases skeletal muscle mass and strength. Biochem Biophys Res Commun. 2003, 300: 965-971.
    19. Zhu X, Topouzis S, Liang LF, Stotish RL. Myostatin signaling through Smad2, Smad3 and Smad4 is regulated by the inhibitory Smad7 by a negative feedback mechanism. Cytokine 2004, 26: 262-272.
    20. Zimmers TA, Davies MV, Koniaris LG, Haynes P, Esquela AF, Tomkinson KN, McPherron AC, Wolfman NM, Lee SJ. Induction of cachexia in mice by systemically administered myostatin. Science 2002, 296: 1486-1488.
    1. Ali A, Nayak DP. Assembly of Sendai virus: M protein interacts with F and HN proteins and with the cytoplasmic tail and transmembrane domain of F protein. Virology 2000, 276: 289-303.
    2. Baer GS, Ebert DH, Chung CJ, Erickson AH and Dermody TS. Mutant cells selected during persistent reovirus infection do not express mature cathepsin L and do not support reovirus disassembly.J Virol 1999, 73: 9532-9543.
    3. Beer C, Andersen DS, Rojek A and Pedersen L. Caveola-dependent endocytic entry of amphotropic murine leukemia virus. J Virol 2005, 79: 10776-10787.
    4. Bordi L, Castilletti C, Falasca L, Ciccosanti F, Calcaterra S, Rozera G, Di Caro A, Zaniratti S, Rinaldi A, Ippolito G, Piacentini M, Capobianchi MR. Bcl-2 inhibits the caspase-dependent apoptosis induced by SARS-CoV without affecting virus replication kinetics.Arch Virol. 2006, 151: 369-377.
    5. Bosch BJ, Martina BEE, van der Zee R, Lepault J, Haijema BJ, Versluis C, Heck AJR, de Groot R, Osterhaus ADME, Rottier PJM. Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides. Proc Natl Acad Sci USA 2004, 101:8455-8460.
    6. Bousarghin L, Touze A, Sizaret PY and Coursaget P. Human papillomavirus types 16, 31, and 58 use different endocytosis pathways to enter cells. J. Virol. 2003, 77: 3846-3850.
    7. Buchholz UJ, Bukreyev A, Yang L, Lamirande EW, Murphy BR, Subbarao K, Collins PL. Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity. Proc. Natl. Acad. Sci. USA 2004, 101: 9804-9809.
    8. Chandran K, Farsetta DL and Nibert ML Strategy for nonenveloped virus entry: a hydrophobic conformer of the reovirus membrane penetration protein micro 1 mediates membrane disruption.J Virol 2002, 76: 9920-9933.
    9. Chandran K, Parker JS, Ehrlich M, Kirchhausen T and Nibert ML. The delta region of outer-capsid protein micro 1 undergoes conformational change and release from reovirus particles during cell entry.J Virol 2003, 77: 13361-13375.
    10. Chandran K, Sullivan NJ, Felbor U, Whelan SP and Cunningham JM. Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection.Science 2005, 308: 1643-1645.
    11. Chazal N, Gerlier D. Virus entry, assembly, budding, and membrane rafts. Microbiol. Mol. Biol. Rev. 2003, 67: 226-237.
    12. Chen H, Hou J, Jiang X, Ma S, Meng M, Wang B, Zhang M, Zhang M, Tang X, Zhang F, Wan T, Li N, Yu Y, Hu H, Yang R, He W, Wang X, Cao X. Response of memory CD8+ T cells to severe acute respiratory syndrome (SARS) coronavirus in recovered SARS patients and healthy individuals. J. Immunol. 2005, 175: 591-598.
    13. Chen JH, Chang YW, Yao CW, Chiueh TS, Huang SC, Chien KY, Chen A, Chang FY, Wong CH, Chen YJ. Plasma proteome of severe acute respiratory syndrome analyzed by two-dimensional gel electrophoresis and mass spectrometry. Proc. Natl. Acad. Sci. USA 2004, 101: 17039-17044.
    14. Cheung CY, Poon LL, Ng IH, Luk W, Sia SF, Wu MH, Chan KH, Yuen KY, Gordon S, Guan Y, Peiris JS. Cytokine responses in severe acute respiratory syndrome coronavirus-infected macrophages in vitro: possible relevance to pathogenesis. J. Virol. 2005, 79: 7819-7826.
    15. Choi KS, Aizaki H, Lai MM. Murine coronavirus requires lipid rafts for virus entry and cell-cell fusion but not for virus release. J. Virol. 2005, 79: 9862-9871.
    16. Cinatl J Jr, Michaelis M, Scholz M, Doerr HW. Role of interferons in the treatment of severe acute respiratory syndrome. Expert. Opin. Biol. Ther. 2004, 4:827-836.
    17. Damm EM, Pelkmans L, Kartenbeck J, Mezzacasa A, Kurzchalia T and Helenius A. Clathrin- and caveolin-1-independent endocytosis: entry of simian virus 40 into cells devoid of caveolae. J Cell Biol 2005, 168:477-488.
    18. Danthi P and Chow M. Cholesterol removal by methyl-beta-cyclodextrin inhibits poliovirus entry. J Virol 2004, 78: 33-41.
    19. Daya M, Cervin M, Anderson R. Cholesterol enhances mouse hepatitis virus-mediated cell fusion. Virology 1988, 163:276-283.
    20. de Groot RJ, Luytjes W, Horzinek MC, van der Zeijst BA, Spaan WJ, Lenstra JA.Evidence for a coiled-coil structure in the spike proteins of coronaviruses. J Mol Biol. 1987, 196: 963-966.
    21. Drosten C, GUnther S, Preiser W, van der Werf S, Brodt H, Becker S, Rabenau H, Panning M, Kolesnikova L, Fouchier RAM, Berger A, Burguière A, Cinatl J, Eickmann M, Escriou N, Grywna K, Kramme S, Manuguerra J, Müller S, Rickerts V, Stürmer M, Vieth S, Klenk H, Osterhaus ADME, Schmitz H, Doerr H W. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med. 2003, 348: 1967-1976.
    22. Ebert DH, Deussing J, Peters C and Dermody TS. J Biol Chem 2002, 277: 24609-24617.
    23. Eckert DM, Kim PS. Design of potent inhibitors of HIV-1 entry from the gp41 N-peptide region. Proc Natl Acad Sci U S A. 2001, 98: 11187-11192.
    24. Empig CJ and Goldsmith MA. Association of the caveola vesicular system with cellular entry by filoviruses. J Virol 2002, 76: 5266-5270.
    25. GlassWG, Subbarao K, Murphy B, Murphy PM. Mechanisms of host defense following severe acute respiratory syndrome-coronavirus (SARS-CoV) pulmonary infection of mice. J. Immunol. 2004,173:4030-4039.
    26. Golden JW, Bahe JA, Lucas WT, Nibert ML and Schiff LA. J Biol Chem 2004, 279: 8547-8557.
    27. Golden JW, Linke J, Schmechel S, Thoemke K and Schiff LA. Addition of exogenous protease facilitates reovirus infection in many restrictive cells. J Virol 2002, 76: 7430-7443.
    28. He R, Leeson A, Andonov A, Li Y, Bastien N, Cao J, Osiowy C, Dobie F, Cutts T, Ballantine M, Li X. Activation of AP-1 signal transduction pathway by SARS coronavirus nucleocapsid protein. Biochem Biophys Res Commun. 2003, 311: 870-876.
    29. He Z, Zhao C, Dong Q, Zhuang H, Song S, Peng G, Dwyer DE. Effects of severe acute respiratory syndrome (SARS) coronavirus infection on peripheral blood lymphocytes and their subsets. Int. J. Infect. Dis. 2005, 9: 323-330.
    30. Helenius A, Kartenbeck J, Simons K, Fries E. On the entry of Semliki forest virus into BHK-21 cells. J Cell Biol 1980, 84: 404-420.
    31. Hommelgaard AM, Roepstorff K, Vilhardt F, Torgersen ML, Sandvig K and van Deurs B. Caveolae: stable membrane domains with a potential for internalization. Traffic 2005, 6: 720-724.
    32. Hon KL, Leung CW, Cheng WT, Chan PK, Chu WC, Kwan YW, Li AM, Fong NC, Ng PC, Chiu MC, Li CK, Tam JS, Fok TF. Clinical presentations and outcome of severe acute respiratory syndrome in children. Lancet 2003, 361: 1701-1703.
    33. Hsueh PR, Huang LM, Chen PJ, Kao CL, Yang PC. Chronological evolution of IgM, IgA, IgG and neutralization antibodies after infection with SARS-associated coronavirus. Clin. Microbiol. Infect.2004, 10:1062-1066.
    34. Huang IC, Bosch BJ, Li F, Li W, Lee KH, Ghiran S, Vasilieva N, Dermody TS, Harrison SC, Dormitzer PR, Farzan M, Rottier PJ, Choe H. SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells. J Biol Chem. 2006, 281: 3198-3203.
    35. Huang KJ, Su IJ, Theron M,Wu YC, Lai SK, Liu CC, Lei HY. An interferon-γ-related cytokine storm in SARS patients. J. Med. Virol. 2005, 75: 185-194.
    36. Inoue Y, Tanaka N, Tanaka Y, Inoue S, Morita K, Min Z, Hattori T, Sugamura K. Ciathrin-dependent Entry of SARS Coronavirus into Target Cells Expressing Cytoplasmic Tail-deleted ACE2. J. Virol. 2007, 81: 8722-8729.
    37. Insel PA, Head BP, Ostrom RS, Patel HH, Swaney JS, Tang CM and Roth DM. Caveolae and lipid rafts: G protein-coupled receptor signaling microdomains in cardiac myocytes. Ann N Y Acad Sci 2005, 1047: 166-172.
    38. Jane-Valbuena J, Breun LA, Schiff LA and Nibert ML Sites and determinants of early cleavages in the proteolytic processing pathway of reovirus surface protein sigma3. J Virol 2002, 76: 5184-5197.
    39. Jeffers SA, Tusell SM, Gillim-Ross L, Hemmila EM, Achenbach JE, Babcock GJ, Thomas WD Jr, Thackray LB, Young MD, Mason RJ, Ambrosino DM, Wentworth DE, Demartini JC, Holmes KV. CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus. Proc Natl Acad Sci U S A. 2004, 101: 15748-15753.
    40. Jiang Y, Xu J, Zhou C, Wu Z, Zhong S, Liu J, Luo W, Chen T, Qin Q, Deng P. Characterization of cytokine/ chemokine profiles of severe acute respiratory syndrome. Am. J. Respir. Crit. Care Med. 2005, 171:850-857.
    41. Kopecky-Bromberg SA, Martinez-Sobrido L, Palese P. 7a protein of severe acute respiratory syndrome coronavirus inhibits cellular protein synthesis and activates p38 mitogen-activated protein kinase. J Virol. 2006, 80: 785-793.
    42. Kozak SL, Heard JM, Kabat D. Segregation of CD4 and CXCR4 into distinct lipid microdomains in T lymphocytes suggests a mechanism for membrane destabilization by human immunodeficiency virus. J. Virol. 2002, 76: 1802-1815.
    43. Ksiazek TG, Erdman D, Goldsmith C, Zaki SR, Peret T, Emery S, Tong S, Urbani C, Comer JA, Lim W, Rollin PE, Nghiem KH, Dowell A Ling S, Humphrey C, Shieh W, Guarner J, Paddock CD, Rota P, Fields B, DeRisi J, Yang J, Cox N, Hughes J, LeDuc JW, Bellini WJ, Anderson LJ, the SARS Working Group. A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med. 2003, 348: 1953-1966.
    44. Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, Huan Y, Yang P, Zhang Y, Deng W, Bao L, Zhang B, Liu G, Wang Z, Chappell M, Liu Y, Zheng D, Leibbrandt A, Wada T, Slutsky AS, Liu D, Qin C, Jiang C, Penninger JM. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005, 11: 875-879.
    45. Lang Z, Zhang L, Zhang S, Meng X, Li J, Song C, Sun L, Zhou Y. Pathological study on severe acute respiratory syndrome. Chin Med J (Engl) 2003, 116: 976-980.
    46. Law HK, Cheung CY,NgHY, Sia SF, Chan YO, Luk W, Nicholls JM, Peiris JS, Lau YL. Chemokine up-regulation in SARS-coronavirus-infected, monocyte-derived human dendritic cells. Blood 2005, 106:2366-2374.
    47. Law PT, Wong CH, Au TC, Chuck CP, Kong SK, Chan PK, To KF, Lo AW, Chan JY, Suen YK, Chan HY, Fung KP, Waye MM, Sung JJ, Lo YM, Tsui SK. The 3a protein of severe acute respiratory syndrome-associated coronavirus induces apoptosis in Vero E6 cells. J Gen Virol. 2005, 86:1921-1930.
    48. Lee CH, Chen RF, Liu JW, Yeh WT, Chang JC, Liu PM, Eng HL, Lin MC, Yang KD. Altered p38 mitogenactivated protein kinase expression in different leukocytes with increment of immunosuppressive mediators in patients with severe acute respiratory syndrome. J. Immunol. 2004, 172:7841-7847.
    49. Leser GP, Lamb RA. Influenza virus assembly and budding in raftderived microdomains: a quantitative analysis of the surface distribution of HA, NA and M2 proteins. Virology 2005, 342: 215-227.
    50. Leung GM, Hedley AJ, Ho LM, Chau P, Wong IO, Thach TQ, Ghani AC, Donnelly CA, Fraser C, Riley S, Ferguson NM, Anderson RM, Tsang T, Leung PY, Wong V, Chan JC, Tsui E, Lo SV, Lam TH. The epidemiology of severe acute respiratory syndrome in the 2003 Hong Kong epidemic: an analysis of all 1755 patients. Ann. Intern. Med. 2004, 141: 662-673.
    51. Li GM, Li YG, Yamate M, Li SM, Ikuta K. Lipid rafts play an important role in the early stage of severe acute respiratory syndrome-coronavirus life cycle. Microbes and Infection 2007, 9: 96-102.
    52. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003, 426: 450- 454.
    53. Liao Z, Graham DR, Hildreth JE. Lipid rafts and HIV pathogenesis: virion-associated cholesterol is required for fusion and infection of susceptible cells. AIDS Res. Hum. Retroviruses 2003, 19: 675-687.
    54. Liu W, Fontanet A, Zhang PH, Zhan L, Xin ZT, Baril L, Tang F, Lv H, Cao WC. Two-year prospective study of the humoral immune response of patients with severe acute respiratory syndrome. J. Infect. Dis. 2006, 193: 792-795.
    55. Manes S, del Real G, Lacalle RA, Lucas P, Gomez-Mouton C, Sanchez-Palomino S, Delgado R, Alcami J, Mira E, Martinez AC. Membrane raft microdomains mediate lateral assemblies required for HIV-1 infection. EMBO Rep. 2000, 1: 190-196.
    56. Marjomaki V, Pietiainen V, Matilainen H, Upla P, Ivaska J, Nissinen L, Reunanen H, Huttunen P, Hyypia T and Heino J. Internalization of echovirus 1 in caveolae. J Virol 2002, 76: 1856-1865.
    57. Marra MA, Jones SJ, Astell CR, Holt RA, Brooks-Wilson A, Butterfield YS, Khattra J, Asano JK, Barber SA, Chan SY, Cloutier A, Coughlin SM, Freeman D, Girn N, Griffith OL, Leach SR, Mayo M, McDonald H, Montgomery SB, Pandoh PK, Petrescu AS, Robertson AG, Schein JE, Siddiqui A, Smailus DE, Stott JM, Yang GS, Plummer F, Andonov A, Artsob H, Bastien N, Bernard K, Booth TF, Bowness D, Czub M, Drebot M, Fernando L, Flick R, Garbutt M, Gray M, Grolla A, Jones S, Feldmann H, Meyers A, Kabani A, Li Y, Normand S, Stroher U, Tipples GA, Tyler S, Vogrig R, Ward D, Watson B, Brunham RC, Krajden M, Petric M, Skowronski DM, Upton C, Roper RL. The genome sequence of the SARS-associated coronavirus. Science 2003, 300: 1399-1404.
    58. Marsh M and Helenius A. Virus entry: open sesame. Cell 2006, 124: 729-740.
    59. Mellman I. Endocytosis and molecular sorting. Annu Rev Cell Dev Biol. 1996, 12:575-625.
    60. Mizutani T, Fukushi S, Murakami M, Hirano T, Saijo M, Kurane I, Morikawa S. Tyrosine dephosphorylation of STAT3 in SARS coronavirus-infected Vero E6 cells. FEBS Lett. 2004, 577: 187-192.
    61. Mizutani T, Fukushi S, Saijo M, Kurane I, Morikawa S. Importance of Akt signaling pathway for apoptosis in SARS-CoV-infected Vero E6 cells. Virology. 2004, 327: 169-174.
    62. Mizutani T, Fukushi S, Saijo M, Kurane I, Morikawa S. Phosphorylation of p38 MAPK and its downstream targets in SARS coronavirus-infected cells. Biochem Biophys Res Commun. 2004, 319: 1228-1234.
    63. National Research Project for SARS, Beijing Group. The involvement of natural killer cells in the pathogenesis of severe acute respiratory syndrome. Am. J. Clin. Pathol. 2004, 121: 507-511.
    64. Ng LF, Hibberd ML, Ooi EE, Tang KF, Neo SY, Tan J, Murthy KR, Vega VB, Chia JM, Liu ET, Ren EC. A human in vitro model system for investigating genome-wide host responses to SARS coronavirus infection. BMC Infect. Dis. 2004, 4:34.
    65. Ng PC, Lam CW, Li AM, Wong CK, Cheng FW, Leung TF, Hon EK, Chan IH, Li CK, Fung KS, Fok TF. Inflammatory cytokine profile in children with severe acute respiratory syndrome. Pediatrics 2004, 113: e7—14.
    66. Nie Y, Wang G, Shi X, Zhang H, Qiu Y, He Z, Wang W, Lian G, Yin X, Du L, Ren L, Wang J, He X, Li T, Deng H, Ding M. Neutralizing antibodies in patients with severe acute respiratory syndrome-associated coronavirus infection. J. Infect. Dis. 2004, 190: 1119-1126.
    67. Odegard AL, Chandran K, Liemann S, Harrison SC and Nibert ML. Disulfide bonding among micro 1 trimers in mammalian reovirus outer capsid: a late and reversible step in virion morphogenesis.J Virol 2003, 77: 5389-5400.
    68. Pelkmans L and Helenius A. Insider information: what viruses tell us about endocytosis. Curr Opin Cell Biol 2003, 15:414-22.
    69. Pelkmans L. Secrets of caveolae- and lipid raft-mediated endocytosis revealed by mammalian viruses. Biochim Biophys Acta 2005, 1746: 295-304.
    70. Pietiainen VM, Marjomaki V, Heino J and Hyypia T. Viral entry, lipid rafts and caveosomes. Ann Med 2005, 37: 394-403.
    71. Poccia F, Agrati C, Castilletti C, Bordi L, Gioia C, Horejsh D, Ippolito G, Chan PK, Hui DS, Sung JJ, Capobianchi MR, Malkovsky M. Anti-severe acute respiratory syndrome coronavirus immune responses: the role played by Vγ9V52 T cells.J. Infect. Dis. 2006, 193:1244-1249.
    72. Popik W, Alce TM, Au WC. Human immunodeficiency virus type 1 uses lipid raft-colocalized CD4 and chemokine receptors for productive entry into CD4 t T cells. J. Virol. 2002, 76: 4709-4722.
    73. Ren L, Yang R, Guo L, Qu J, Wang J, Hung T. Apoptosis induced by the SARS-associated coronavirus in Vero cells is replication-dependent and involves caspase. DNA Cell Biol. 2005, 24: 496-502.
    74. Reyes-Del Valle J, Chavez-Salinas S, Medina F, Del Angel RM. Heat shock protein 90 and heat shock protein 70 are components of dengue virus receptor complex in human cells. J. Virol. 2005, 79:4557-4567.
    75. Rota PA, Oberste MS, Monroe SS, Nix WA, Campagnoli R, Icenogle JP, Penaranda S, Bankamp B, Maher K, Chen MH, Tong S, Tamin A, Lowe L, Frace M, DeRisi JL, Chen Q, Wang D, Erdman DD, Peret TC, Burns C, Ksiazek TG, Rollin PE, Sanchez A, Liffick S, Holloway B, Limor J, McCaustland K, Olsen-Rasmussen M, Fouchier R, Günther S, Osterhaus AD, Drosten C, Pallansch MA, Anderson LJ, Bellini WJ. Characterization of a novel coronavirus associated with severe acute respiratory syndrome, Science 2003, 300: 1394-1399.
    76. Sieczkarski SB and Whittaker GR. Characterization of the host cell entry of filamentous influenza virus. Arch Virol 2005, 150: 1783-1796.
    77. Simmons G, Gosalia DN, Rennekamp AJ, Reeves JD, Diamond SL, Bates P. Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. Proc Natl Acad Sci U S A. 2005, 102: 11876-11881.
    78. Simmons G, Reeves JD, Rennekamp AJ, Amberg SM, Piefer AJ, Bates P. Characterization of severe acute respiratory syndrome-associated coronavirus (SARS CoV) spike glycoprotein-mediated viral entry. Proc Natl Acad Sci USA 2004, 101: 4240-4245.
    79. Spiegel M, Pichlmair A, Martínez-Sobrido L, Cros J, García-Sastre A, Haller O, Weber F. Inhibition of beta interferon induction by severe acute respiratory syndrome coronavirus suggests a two-step model for activation of interferon regulatory factor 3. J Virol. 2005, 79: 2079-2086.
    80. Stang E, Blystad FD, Kazazic M, Bertelsen V, Brodahl T, Raiborg C, Stenmark H and Madshus IH. Cbl-dependent ubiquitination is required for progression of EGF receptors into clathrin-coated pits. Mol Biol Cell 2004, 1996, 15: 3591-3604.
    81. Stuart AD, Eustace HE, McKee TA, Brown TD. A novel cell entry pathway for a DAF-using human enterovirus is dependent on lipid rafts. J. Virol. 2002, 76: 9307-9322.
    82. Sturzenbecker LJ, Nibert M, Furlong D and Fields BN. Intracellular digestion of reovirus particles requires a low pH and is an essential step in the viral infectious cycle. J Virol 1987, 61: 2351-2361.
    83. Sun X, Yau VK, Briggs BJ and Whittaker GR. Role of clathrin-mediated endocytosis during vesicular stomatitis virus entry into host cells. Virology 2005, 338: 53-60.
    84. Supekar VM, Bruckmann C, Ingallinella P, Bianchi E, Pessi A, Carfi A. Structure of a proteolytically resistant core from the severe acute respiratory syndrome coronavirus S2 fusion protein. Proc Natl Acad Sci USA 2004, 101: 17958-17963.
    85. Surjit M, Liu B, Jameel S, Chow VT, Lal SK. The SARS coronavirus nucleocapsid protein induces actin reorganization and apoptosis in COS-1 cells in the absence of growth factors. Biochem J. 2004,383: 13-18.
    86. Takeda M, Leser GP, Russell CJ, Lamb RA. Influenza virus hemagglutinin concentrates in lipid raft microdomains for efficient viral fusion. Proc. Natl. Acad. Sci. USA 2003, 100: 14610-14617.
    87. Tan YJ, Fielding BC, Goh PY, Shen S, Tan TH, Lim SG, Hong W. Overexpression of 7a, a protein specifically encoded by the severe acute respiratory syndrome coronavirus, induces apoptosis via a caspase-dependent pathway. J Virol. 2004, 78: 14043-14047.
    88. Tang NL, Chan PK,Wong CK, To KF,Wu AK, Sung YM, Hui DS, Sung JJ, Lam CW. Early enhanced expression of interferon-inducible protein-10 (CXCL-10) and other chemokines predicts adverse outcome in severe acute respiratory syndrome. Clin. Chem. 2005, 51: 2333-2340.
    89. Thorp EB, Gallagher TM. Requirements for CEACAMs and cholesterol during murine coronavirus cell entry. J. Virol. 2004, 78: 2682-2692.
    90. Tseng CT, Perrone LA, Zhu H, Makino S, Peters CJ. Severe acute respiratory syndrome and the innate immune responses: modulation of effector cell function without productive infection. J. Immunol. 2005, 174: 7977-7985.
    91. Turk V, Turk B and Turk D. Lysosomal cysteine proteases: facts and opportunities.Embo J 2001, 20: 4629-4633.
    92. Wang P, Chen J, Zheng A, Nie Y, Shi X, Wang W, Wang G, Luo M, Liu H, Tan L, Song X, Wang Z, Yin X, Qu X, Wang X, Qing T, Ding M, Deng H. Expression cloning of functional receptor used by SARS coronavirus. Biochem Biophys Res Commun. 2004, 315: 439-444.
    93. Wang X, Huang DY, Huong SM, Huang ES. Integrin ab3 is a coreceptor for human cytomegalovirus. Nat. Med. 2005, 11: 515-521.
    94. Wang YD, Sin WY, Xu GB, Yang HH, Wong TY, Pang XW, He XY, Zhang HG, Ng JN, Cheng CS, Yu J, Meng L, Yang RF, Lai ST, Guo ZH, Xie Y, Chen WF. T-cell epitopes in severe acute respiratory syndrome (SARS) coronavirus spike protein elicit a specific T-cell immune response in patients who recover from SARS. J. Virol. 2004, 78: 5612-5618.
    95. Wong CK, Lam CW, Wu AK, Ip WK, Lee NL, Chan IH, Lit LC, Hui DS, Chan MH, Chung SS, Sung JJ. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin. Exp. Immunol. 2004, 136: 95-103.
    96. Wong RS,Wu A, To KF, Lee N, Lam CW, Wong CK, Chan PK, Ng MH, Yu LM, Hui DS, Tarn JS, Cheng G, Sung JJ. Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis. BMJ 2003, 326:1358-1362.
    97. Xu Y, Lou Z, Liu Y, Pang H, Tien P, Gao GF, Rao Z. Crystal structure of severe acute respiratory syndrome coronavirus spike protein fusion core. J Biol Chem. 2004, 279: 49414-49419.
    98. Yan H, Xiao G, Zhang J, Hu Y, Yuan F, Cole DK, Zheng C, Gao GF. SARS coronavirus induces apoptosis in Vero E6 cells. J Med Virol. 2004, 73: 323-331.
    99. Yang Y, Xiong Z, Zhang S, Yan Y, Nguyen J, Ng B, Lu H, Brendese J, Yang F, Wang H, Yang XF. Bcl-xL inhibits T-cell apoptosis induced by expression of SARS coronavirus E protein in the absence of growth factors. Biochem J. 2005, 392:135-143.
    100. Yilla M, Harcourt BH, Hickman CJ, McGrew M,Tamin A, Goldsmith CS, Bellini WJ, Anderson LJ. SARS-coronavirus replication in human peripheral monocytes/macrophages. Virus Res. 2005, 107:93-101.
    101. Yuan K, Yi L, Chen J, Qu X, Qing T, Rao X, Jiang P, Hu J, Xiong Z, Nie Y, Shi X,WangW, Ling C, Yin X, Fan K, Lai L, Ding M, Deng H. Suppression of SARS-CoV by peptides corresponding to heptad regions on spike glycoprotein. Biochem Biophys Res Commun 2004, 319: 746-752.
    102. Zhang Q, Cui J, Huang X, Zheng H, Huang J, Fang L, Li K, Zhang J. The life cycle of SARS coronavirus in Vero E6 cells. J Med Virol 2004, 73: 332-337.
    103. Zhang QL, Ding YQ, He L, WangW, Zhang JH, Wang HJ, Cai JJ,Geng J, Lu YD, Luo YL. Detection of cell apoptosis in the pathological tissues of patients with SARS and its significance. Di Yi Jun Yi Da Xue Xue Bao 2003, 23: 770-773.
    104. Zhang Y, Li J, Zhan Y, Wu L, Yu X, Zhang W, Ye L, Xu S, Sun R, Wang Y, Lou J. Analysis of serum cytokines in patients with severe acute respiratory syndrome. Infect. Immun. 2004, 72: 4410-4415.
    105. Zhao G, Shi SQ, Yang Y, Peng JP. M and N proteins of SARS coronavirus induce apoptosis in HPF cells. Cell Biol Toxicol. 2006,22: 313-322.
    106. Zheng YH, Plemenitas A, Linnemann T, Fackler OT, Peterlin BM. Nef increases infectivity of HIV via lipid rafts. Curr. Biol. 2001, 11: 875-879.

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