成功大學博碩士論文系統

簡易檢索 / 詳目顯示

回結果列表

研究生：	孫宏羽 Sun, Hong-yu
論文名稱：	鑑定由C型肝炎病毒感染病患中所分離之病毒-脂質顆粒 Characterization of viral-lipid particles isolated from patients with hepatitis C virus infection
指導教授：	張定宗 Chang, Ting-Tsung 楊孔嘉 Young, Kung-Chia
學位類別：	碩士 Master
系所名稱：	醫學院 - 分子醫學研究所 Institute of Molecular Medicine
論文出版年：	2004
畢業學年度：	92
語文別：	英文
論文頁數：	126
中文關鍵詞：	C型肝炎病毒，低密度脂蛋白，病毒-脂質顆粒
外文關鍵詞：	LDL, viral-lipid particle, HCV
相關次數：	點閱：124 下載：1
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

　　C型肝炎病毒(HCV)隸屬於黃熱病毒科，是具有外套膜的病毒，帶有一段大約9.6kb正股的RNA作為遺傳物質。由於C型肝炎病毒無法在體外被培養，因此有關C型肝炎病毒如何進入細胞以及如何造成慢性感染的機制一直尚未了解。除了利用本身的病毒顆粒藉由體液循環來感染細胞之外，C型肝炎病毒目前被認為可以藉由黏附在一些來自細胞的物質上來感染周邊組織及細胞。在病人的血液樣本中，極低密度脂蛋白(VLDL)及低密度脂蛋白(LDL)已經被證實與C型肝炎病毒顆粒有直接的交互作用；而且在具有感染性的C型肝炎病毒顆粒中扮演極為重要的角色。與C型肝炎病毒顆粒相關的低密度/極低密度脂蛋白可能模擬與細胞表面受體結合的受質來協助病毒進入細胞，至少有一部分是透過內噬作用(endocytosis)進入到細胞內。然而與C型肝炎病毒顆粒相關的低密度/極低密度脂蛋白有關的蛋白質成分仍然還未被深入的探討，因此本實驗的目標即是想從感染C型肝炎病毒病人的血液樣本中分離出與C型肝炎病毒顆粒相關的低密度/極低密度脂蛋白，並進一步鑑定可能與C型肝炎病毒感染有關的宿主蛋白。利用梯度離心的方式將來自病人的血液樣本純化出低密度/極低密度脂蛋白，並利用電泳及生化分析來確認這些純化出來的物質；經過純化的病毒-脂質顆粒之病毒定量結果顯示來自C型肝炎病人的低密度/極低密度脂蛋白較來自感染B型肝炎病毒及健康對照組的低密度/極低密度脂蛋白帶有較高比例的病毒量。核糖核酸酶敏感性實驗的結果顯示C型肝炎病毒-脂質顆粒中的脂質成分可能會保護C型肝炎病毒的RNA。相似的結果也出現在低密度/極低密度脂蛋白的免疫球蛋白定量上，而酵素連結免疫吸附測試(ELISA)證實了HCV病毒-脂質顆粒表面帶有免疫球蛋白。為了進一步探討HCV病毒-脂質顆粒蛋白質特徵，利用二維電泳及質譜儀分析帶有低密度/極低密度脂蛋白的低密度層；初步的結果顯示，來自C型肝炎病毒感染的低密度/極低密度脂蛋白則具有與正常對照組不同的蛋白質組成，而來自B型肝炎病毒感染的低密度/極低密度脂蛋白的蛋白質組成成分則與正常對照組相當類似。蛋白質鑑定的結果顯示C型肝炎病毒-脂質顆粒含有某些未被命名的蛋白質，值得進一步的去分析。綜合以上結果，本實驗已能成功的從感染C型肝炎病人的血液樣本中分離出帶有C型肝炎病毒-脂質顆粒，實驗數據也顯示這些病毒-脂質顆粒帶有較高的病毒RNA以及免疫球蛋白，而病毒-脂質顆粒的脂肪成分可以保護C型肝炎病毒RNA進而延長RNA的存活時間；此外，來自於感染C型肝炎的患者所純化出的病毒-脂質顆粒之蛋白質特徵與感染B型肝炎的患者及健康對照組所表現出的蛋白質特徵也有所不同。

　　Hepatitis C virus （HCV） an enveloped virus with a positive single-stranded RNA genome of about 9.6 kb, belongs to the Flaviviridae family. The mechanisms of HCV entry and then leading to a persistent viral infection in host cells were poorly understood because the lack of an efficient experimental HCV cultivated system. HCV viruses were currently proposed to process an ability of adherence to cellular factors, besides free viral particles circulate in peripheral circulation. Low-and very low-density lipoproteins (LDL and VLDL) had been shown to directly interact with HCV particles, which functions as the most important part of infectious HCV virions in blood sample from patients. The LDL/VLDL-associated HCV virions might mimic as ligand binding to cell surface receptor for viral entry by, at least in part, endocytosis. However, the protein components in complex with LDL/VLDL-associated HCV virions had not yet been identified. This study aims to isolate circulating LDL/VLDL associated HCV virions and to identify the virion-associated host proteins, which hypothetically facilitate virus infection. The low-density fractions from patients’ blood samples were purified with gradient centrifugation and confirmed by electrophoresis and biochemical analysis. The viral genome quantification of those purified viral-lipid particles revealed that the proportion of viral titer in HCV low-density fraction was significantly higher than the corresponding fraction in HBV samples. The RNase sensitivity assay revealed that the lipid component might provide protection of HCV RNA in viral lipid particle. The similar result was appeared in quantification of immunoglobulin of low-density fractions. ELISA assay demonstrated that the HCV viral-lipid particles consist of immunoglobulin. In order to identify the protein profile in HCV viral-lipid particles, the low-density fractions were explored for 2D gel separation technology coupled to mass spectrometry analysis. The preliminary data showed HCV viral-lipid particles encompass some proteins different from the corresponding HBV fraction, which was similar to those from healthy donor. Protein identification revealed that some proteins belonged to unnamed protein products and these proteins should be further characterized. Taken together, HCV viral-lipid particles could be isolated from HCV-infected samples and the data indicated that high concentration of viral load and immunoglobulin had been found in HCV viral-lipid particle. The lipid component of HCV viral-lipid particle prolonged the half life of HCV RNA and might facilitate HCV infection. In addition, the protein profile of HCV viral-lipid particle differed from those in the counterparts from HBV patients and normal controls.

Abstract (in Chinese)                                        I
Abstract (in English)                                        III
Acknowledgements                                             V
Index                                                        VI
Figures / Tables                                             IX
Reagents and Instruments                                     XI
Chapter 1: Introduction                                      1
I.	The epidemiology of HCV                              3
II.	The molecular virology of HCV                        6
III.	The pathogenesis and treatment of HCV                13
IV.	Lipid metabolism and HCV infection                   17
V.	Goal and strategy of this Study                      20
 
Chapter 2: Materials and Methods                             22 
Part I: Isolation of low-density fractions from blood samples
I.	Preparation of blood samples                         24
II.	Gradient ultracentrifugation                         24

Part II: Clinical analysis of blood samples and low-density fractions
I.	Agarose gel electrophoresis                          26
II.	High density lipoprotein (HDL) quantification        28
III.	Triglycerides (TG) quantification                    28
IV.	Cholesterol quantification                           28
V.	Low-density lipoprotein (LDL) quantification         29
VI.	Immunoglobin G (IgG) quantification of blood samples 29

Part III: Viral quantification and qualitation
I.	HCV RNA extraction                                   30
II.	HCV qualitative analysis                             32
III.	Quantification of HCV RNA by real-time PCR           36
IV.	HBV DNA extraction                                   38
V.	HBV qualitative analysis                             40
VI.	Quantification of HBV DNA by real-time PCR           41

Part IV: Characterization of viral-lipid particles
I.	Immunoblotting                                       43
II.	RNase sensitivity assay                              47
III.	Functional assay of HCV viral-lipid particles        49
IV.	Two dimensional PAGE analysis                        53
V.	Protein identification                               60

Chapter 3: Results                                           61
Part I: Isolation of low-density fractions from              63
       blood samples        
Part II: Biochemical analysis of blood samples and low-density 
fractions
I.	TG, LDL, and CHO quantification of samples           63
II.	Viral titer quantification                           64
III.	Immunoglobin (IgG) detection                         65

Part III: Systematic analysis of low-density fractions isolated
 from HCV-infected patients and healthy donors
I.	Sample collection                                    65
II.	Biochemical analysis of samples                      66
III.	Immunoglobulin quantification                        66
IV.	Viral titer quantification by real-time PCR          68

Part IV: Characterization of viral-lipid particles
I.	RNase sensitivity assay                              68
II.	Functional assay of HCV viral-lipid particles        69
III.	Two dimensional gel analysis                         69

Chapter 4: Discussion                                        72
Part I: Isolation and characterization of low-density        73
fraction from human blood samples                                  
Part II: Systematic analysis of low-density fractions        74
isolated from HCV-infected patients and healthy donors              
Part III: Characterization of viral-lipid particles          76

References                                                   80
Figures/Tables                                               90
Author                                                       109

                                    

1. Wasley A, Alter MJ. Epidemiology of hepatitis C: geographic differences and temporal trends. Semin Liver Dis 2000; 20:1-16.

2. Chen DS, Kuo G, Sung JL, Lai MY, Sheu JC, Chen PJ, Yang PM, Hsu HM, Chang MH, Chen CJ, Hahn LC, Choo QL, Wang TH, Houghton M. Hepatitis C virus infection in an area hyperendemic for hepatitis B and chronic liver disease: the Taiwan experience. Infect Dis 1990; 162:817-822.

3. Third National Health and Nutrition Examination Survey (NHANES III). National Center for Health Statistics (CD-ROM Catalog No. PB97-502959), United States, 1995. Hyattsville, Maryland: Public Health Service. 1996.

4. Armstrong GL, Alter MJ, McQuillan GM, et al. The past incidence of hepatitis C virus infection: implications for the future burden of chronic liver disease in the United States. Hepatology 2000; 31:777-82.

5. Tommy Yen, M.D., Emmet B. Keeffe, M.D., and Aijaz Ahmed, M.D. The Epidemiology of Hepatitis C Virus Infection. J Clin Gastroenterol 2003; 36(1):47-53.

6. Thorpe LE, Ouellet LJ, Levy JR, et al. Hepatitis C virus infection: prevalence, risk factors, and prevention opportunities among young injection drug users in Chicago.1997-1999. J Infect Dis 2000; 182:1588-94.

7. Garfein RS. Vlahov D. Galai N, et al. Viral infections in short-term injection drug users: the prevalence of the hepatitis C, hepatitis B, human immunodeficiency, and human T-lymphotropic viruses. Am J Public Health 1996; 86:655-61.
.
8. Donahue JG, Munoz A, Ness PM, et al. The declining risk of post-transfusion hepatitis C virus infection. N Engl J Med 1992; 327:369-73

9. Pereira BJ, Levey AS. Hepatitis C virus infection in dialysis and renal transplantation. Kidney Int 1997; 51:981-99.

10. Carvalho M, Branco PB, Luvizotto ML, et al. High prevalence of hepatitis Cvirus infection in chronic hemodialysis patients. Braz J Infect Dis 1999; 3:144-8.

11. Thomas DL, Gruninger SE, Siew C, et al. Occupational risk of hepatitis infections among general dentists and oral surgeons in North America. Am J Med 1996; 100:41-5.

12. Alter MJ, Coleman PJ, Alexander WJ, et al. Importance of heterosexual activity in the transmission of hepatitis B and non-A, non-B hepatitis. JAMA 1989; 262: 1201-5.

13. Piazza M, Sagliocca L, Tosone G, et al. Sexual transmission of the hepatitis C virus and efficacy of prophylaxis with intramuscular immune serum globulin. A randomized controlled trial. Arch Intern Med 1997; 157:1537-44.

14. Tajiri H, Miyoshi Y, Funada S, et al. Prospective study of mother-to-infant transmission of hepatitis C virus. Pediatr Infect Dis J 2001; 20:10-4.

15. Lin HH, Kao JH, Hsu HY, et al. Least microtransfusion from mother to fetus in elective cesarean delivery. Obstet Gynecol 1996; 87:244-8.

16. Kassem AS, el-Nawawy AA, Massoud MN, et al. Prevalence of hepatitis C virus HCV) infection and its vertical transmission in Egyptian pregnant women and their newborns. J Trop Pediatr 2000; 46:231-3.

17. Choo QL, Kuo G, Weiner AJ, Bradley LRDW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A non-B viral hepatitis genome. Science 1989; 244:359-362.

18. Wang C, Sarnow P, Siddiqui A. Translation of human hepatitis C virus RNA in cultured cells is mediated by an internal ribosome-binding mechanism. J Virol 1993; 67(6):3338-44.

19. Anwar A, Ali N, Tanveer R, Siddiqui A. Demonstration of functional requirement of polypyrimidine tract-binding protein by SELEX RNA during hepatitis C virus internal ribosome entry site-mediated translation initiation. J Biol Chem 2000; 275(44):34231-5.

20. Ali N, Pruijn GJ, Kenan DJ, Keene JD, Siddiqui A. Human La antigen is required for the hepatitis C virus internal ribosome entry site-mediated translation. J Biol Chem 2000; 275(36):27531-40.

21. Kolykhalov AA, Feinstone SM, Rice CM. Identification of a highly conserved sequence element at the 3' terminus of hepatitis C virus genome RNA. J Virol 1996; 70(6):3363-71.

22. Tsuchihara K, Tanaka T, Hijikata M, Kuge S, Toyoda H, Nomoto A, Yamamoto N, Shimotohno K. Specific interaction of polypyrimidine tract-binding protein with the extreme 3'-terminal structure of the hepatitis C virus genome, the 3'X. J Virol 1997; 71(9):6720-6.

23. Spangberg K, Wiklund L, Schwartz S. Binding of the La autoantigen to the hepatitis C virus 3' untranslated region protects the RNA from rapid degradation in vitro. J Gen Viro. 2001; 82(Pt 1):113-20.

24. Hijikata M, Mizushima H, Akagi T, Mori S, Kakiuchi N, Kato N, Tanaka T, Kimura K, Shimotohno K. Two distinct proteinase activities required for the processing of a putative nonstructural precursor protein of hepatitis C virus. J Virol 1993; 67(8):4665-75.

25. Failla C, Tomei L, De Francesco R. Both NS3 and NS4A are required for proteolytic processing of hepatitis C virus nonstructural proteins. J Virol 1994; 68(6):3753-60.

26. Fan Z, Yang QR, Twu JS, Sherker AH. Specific in vitro association between the hepatitis C viral genome and core protein. J Med Virol 1999; 59(2):131-4.

27. Barba G, Harper F, Harada T, Kohara M, Goulinet S, Matsuura Y, Eder G, Schaff Z, Chapman MJ, Miyamura T, Brechot C. Hepatitis C virus core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets. Proc Natl Acad Sci U S A 1997; 94(4):1200-5.

28. Ray RB, Lagging LM, Meyer K, Ray R. Hepatitis C virus core protein cooperates with ras and transforms primary rat embryo fibroblasts to tumorigenic phenotype. J Virol 1996; 70(7):4438-43.

29. Moriya K, Fujie H, Shintani Y, Yotsuyanagi H, Tsutsumi T, Ishibashi K, Matsuura Y, Kimura S, Miyamura T, Koike K. The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat Med1998; 4(9):1065-7.

30. Lin C, Lindenbach BD, Pragai BM, McCourt DW, Rice CM. Processing in the hepatitis C virus E2-NS2 region: identification of p7 and two distinct E2-specific products with different C termini. J Virol 1994; 68(8):5063-73.

31. Pavlovic D, Neville DC, Argaud O, Blumberg B, Dwek RA, Fischer WB, Zitzmann N. The hepatitis C virus p7 protein forms an ion channel that is inhibited by long-alkyl-chain iminosugar derivatives. Proc Natl Acad Sci U S A 2003; 100(10):6104-8.

32. Anne Op De Beeck, Roland Montserret, Sandrine Duvet, Laurence Cocquerel, René Cacan, Benoît Barberot, Marc Le Maire, François Penin, and Jean Dubuisson. The Transmembrane Domains of Hepatitis C Virus Envelope Glycoproteins E1 and E2 Play a Major Role in Heterodimerization. J. Biol. Chem 2000; 275: 31428 - 31437.

33. R. De Francesco, C. Steinkuhler. Structure and function of the hepatitis C virus NS3-NS4A serine proteinase. Curr Top Microbiol Immunol 2000; 242:149-69. Review.

34. Bartenschlager R, Ahlborn-Laake L, Yasargil K, Mous J, Jacobsen H. Substrate determinants for cleavage in cis and in trans by the hepatitis C virus NS3 proteinase. J Virol 1995; 69(1):198-205.

35. Borowski P, Heiland M, Feucht H, Laufs R. Characterisation of non-structural protein 3 of hepatitis C virus as modulator of protein phosphorylation mediated by PKA and PKC: evidences for action on the level of substrate and enzyme. Arch Virol 1999; 144(4):687-701.

36. Kwun HJ, Jung EY, Ahn JY, Lee MN, Jang KL. p53-dependent transcriptional repression of p21(waf1) by hepatitis C virus NS3. J Gen Virol 2001; 82(Pt 9):2235-41.

37. Park JS, Yang JM, Min MK. Hepatitis C virus nonstructural protein NS4B transforms NIH3T3 cells in cooperation with the Ha-ras oncogene. Biochem Biophys Res Commun 2000; 267(2):581-7.

38. Enomoto N, Sakuma I, Asahina Y, Kurosaki M, Murakami T, Yamamoto C, Ogura Y, Izumi N, Marumo F, Sato C. Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection. N Engl J Med 1996; 334(2):77-81.

39. Gale M Jr, Blakely CM, Kwieciszewski B, Tan SL, Dossett M, Tang NM, Korth MJ, Polyak SJ, Gretch DR, Katze MG. Control of PKR protein kinase by hepatitis C virus nonstructural 5A protein: molecular mechanisms of kinase regulation. Mol Cell Biol 1998; 18(9):5208-18.

40. Arima N, Kao CY, Licht T, Padmanabhan R, Sasaguri Y, Padmanabhan R. Modulation of cell growth by the hepatitis C virus nonstructural protein NS5A. J Biol Chem 2001; 276(16):12675-84.

41. Majumder M, Ghosh AK, Steele R, Ray R, Ray RB. Hepatitis C virus NS5A physically associates with p53 and regulates p21/waf1 gene expression in a p53-dependent manner. J Virol 2001; 75(3):1401-7.

42. Ghosh AK, Majumder M, Steele R, Yaciuk P, Chrivia J, Ray R, Ray RB. Hepatitis C virus NS5A protein modulates transcription through a novel cellular transcription factor SRCAP. J Biol Chem 2000; 275(10):7184-8.

43. Ghosh AK, Steele R, Meyer K, Ray R, Ray RB. Hepatitis C virus NS5A protein modulates cell cycle regulatory genes and promotes cell growth. J Gen Virol 1999; 80 ( Pt 5):1179-83.

44. Song J, Nagano-Fujii M, Wang F, Florese R, Fujita T, Ishido S, Hotta H. Nuclear localization and intramolecular cleavage of N-terminally deleted NS5A protein of hepatitis C virus. Virus Res 2000; 69(2):109-17.

45. Hong Tu, Lu Gao, Stephanie T. Shi, Deborah R. Taylor, Tao Yang, Austin K. Mircheff, Yumei Wen, Alexander E. Gorbalenya, Soon B. Hwang and Michael M. C. Lai. Hepatitis C Virus RNA Polymerase and NS5A Complex with a SNARE-like Protein. Virology 1999; 263, 30-41.

46. Major ME, Rehermann B, Feinstone SM.: Knipe DM, Howley PM, Chanock RM, Monath TP, Roizman B, Straus SE, editors. Hepatitis C viruses. In Fields virology. 4th ed. Philadelphia: Lippincott-Raven, 2001.

47. Yoneyama M, Suhara W, Fukuhara Y, Fukuda M, Nishida E, Fujita T. Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/p300. EMBO J 1998; 17:1087-95.

48. Lanford RE, Bigger C, Bassett S, Klimpel G. The chimpanzee model of hepatitis C virus infections. ILAR J 2001; 42:117-26.

49. Kusano F, Tanaka Y, Marumo F, Sato C. Expression of C-C chemokines is associated with portal and periportal inflammation in the liver of patients with chronic hepatitis C. Lab Invest 2000; 80:415-22.

50. Ramsay AJ, Ruby J, Ramshaw IA. A case for cytokines as effector molecules in the resolution of virus infection. Immunol Today 1993; 14:155-7.

51. Urban JF Jr, Katona IM, Paul WE, Finkelman FD. Interleukin 4 is important in protective immunity to a gastrointestinal nematode infection in mice. Proc Natl Acad Sci USA 1991; 88:5513-7.

52. Zajac AJ, Quinn DG, Cohen PL, Frelinger JA. Fas-dependent CD4+ cytotoxic T-cell-mediated pathogenesis during virus infection. Proc Natl Acad Sci U S A 1996; 93:14730-5.

53. Tsai SL, Liaw YF, Chen MH, Huang CY, Kuo GC. Detection of type 2-like T-helper cells in hepatitis C virus infection: implications for hepatitis C virus chronicity. Hepatology 1997; 25:449-58.

54. Gruener NH, Gerlach TJ, Jung MC, Diepolder HM, Schirren CA, Schraut WW, et al. Association of hepatitis C virus-specific CD8+ T cells with viral clearance in acute hepatitis C. J Infect Dis 2000; 181:1528-36.

55. Lindsay KL. Therapy of hepatitis C: Overview. Hepatology 1997; 26:715-755.

56. Zeuzem S, Feinman SV, Rasenack J, Heathcote EJ, Lai MY, Gane E, O'Grady J, Reichen J, Diago M, Lin A, Hoffman J, Brunda MJ. Peginterferon alfa-2a in patients with chronic hepatitis C. N Engl J Med 2000; 343(23):1666-72.

57. Keating GM, Curran MP. Peginterferon-alpha-2a (40kD) plus ribavirin: a review of its use in the management of chronic hepatitis C. Drugs 2003; 63(7):701-30.

58. Thomssen R, Bonk S, Thiele A. Density heterogeneities of hepatitis C virus in human sera due to the binding of beta-lipoproteins and immunoglobulins. Med Microbiol Immunol (Berl) 1993; 182(6):329-34.

59. Monazahian M, Bohme I, Bonk S, Koch A, Scholz C, Grethe S, Thomssen R. Low density lipoprotein receptor as a candidate receptor for hepatitis C virus. J Med Virol 1999; 57(3):223-9.

60. Sabile A, Perlemuter G, Bono F, Kohara K, Demaugre F, Kohara M, Matsuura Y, Miyamura T, Brechot C, Barba G. Hepatitis C virus core protein binds to apolipoprotein AII and its secretion is modulated by fibrates. Hepatology 1999; 30(4):1064-76.

61. Lerat H, Honda M, Beard MR, Loesch K, Sun J, Yang Y, Okuda M, Gosert R, Xiao SY, Weinman SA, Lemon SM. Steatosis and liver cancer in transgenic mice expressing the structural and nonstructural proteins of hepatitis C virus. Gastroenterology 2002; 122(2):352-65.

62. Wetterau JR, Aggerbeck LP, Bouma ME, Eisenberg C, Munck A, Hermier M, Schmitz J, Gay G, Rader DJ, Gregg RE. Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Science 1992; 258(5084):999-1001.

63. Wang L, Fast DG, Attie AD. The enzymatic and non-enzymatic roles of protein-disulfide isomerase in apolipoprotein B secretion. J Biol Chem 1997; 272(44):27644-51.

64. Shelness, G. S., M. F. Ingram, X. F. Huang, and J. A. DeLozier. Apolipoprotein B in the rough endoplasmic reticulum: translation, translocation and the initiation of lipoprotein assembly. J. Nutr 1999; 129:456S-462S.

65. Rustaeus, S., K. Lindberg, P. Stillemark, C. Claesson, L. Asp, T. Larsson, J. Boren, and S. O. Olofsson.. Assembly of very low density lipoprotein: a two-step process of apolipoprotein B core lipidation. J. Nutr 1999; 129:463S- 466S.

66. Agnello, V., G. Abel, M. Elfahal, G. B. Knight, and Q.-X. Zhang. Hepatitis C virus and other Flaviviridae viruses enter cells via low density lipoprotein receptor. Proc. Natl. Acad. Sci. USA 1999; 96:12766-12771.

67. Wunschmann, S., J. D. Medh, D. Klinzmann, W. N. Schmidt, and J. T. Stapleton. Characterization of hepatitis C virus (HCV) and HCV E2 interactions with CD81 and the low-density lipoprotein receptor. J. Virol 2000; 74:10055-10062.

68. P. Andre´, F. Komurian-Pradel, S. Deforges, M. Perret, J. L. Berland, M. Sodoyer, S. Pol, C. Bre´chot, G. Paranhos-Baccala`, and V. Lotteau. Characterization of Low- and Very-Low-Density Hepatitis C Virus RNA-Containing Particles. J. Virol 2002; 76. 6919-6928.

69. Carrick, R. J., G. G. Schlauder, D. A. Peterson, and I. K. Mushahwar. Examination of the buoyant density of hepatitis C virus by the polymerase chain reaction. J. Virol. Methods 1992; 39:279-289.

70. Miyamoto, H., H. Okamoto, K. Sato, T. Tanaka, and S. Mishiro. Extraordinarily low density of hepatitis C virus estimated by sucrose density gradient centrifugation and the polymerase chain reaction. J. Gen. Virol 1992; 73:715-718.

71. Prince, A. M., T. Huima-Byron, T. S. Parker, and D. M. Levine. Visualization of hepatitis C virions and putative defective interfering particles isolated from low-density lipoproteins. J. Viral Hepatol 1996; 3:11-17.

72. Hijikata, M., Y. K. himizu, H. Kato, A. Iwamoto, J. W. Shih, H. J. Alter, R. H. Purcell, and H. Yoshikura. Equilibrium centrifugation studies of hepatitis C virus: evidence for circulating immune complexes. J. Virol 1993; 67: 1953-1958.

73. Vincent Agnello, Gyo¨ rgy ´ Abel, Mutasim Elfahal, Glenn B. Knight, and Qing-Xiu Zhang. Hepatitis C virus and other Flaviviridae viruses enter cells via low density lipoprotein receptor. PNAS 1999; 96. 12766–12771

74. Marino R, Deibis L, De Sanctis JB, Bianco NE, Toro F. Interaction of immune complexes isolated from hepatitis C virus-infected individuals with human cell lines. Med Microbiol Immunol (Berl) 2004. [Epub ahead of print]

75. Jennifer E. Garrus, Uta K. von Schwedler, Owen W. Pornillos, Scott G. Morham, Kenton H. Zavitz, Hubert E. Wang, Daniel A. Wettstein, Kirsten M. Stray, Mélanie Coté, Rebecca L. Rich, David G. Myszka, and Wesley I. Sundquist. Tsg101 and the Vacuolar Protein Sorting Pathway Are Essential for HIV-1 Budding. Cell 2001; 107: 55-65.

76. Itzhaki RF, Lin WR, Shang D, Wilcock GK, Faragher B, Jamieson GA. Herpes simplex virus type 1 in brain and risk of Alzheimer’s disease. Lancet 1997;349:241-244.

77. Lin WR, Graham J, MacGowan SM, Wilcock GK, Itzhaki RF. Alzheimer’s disease, herpes virus in brain, apolipoprotein E4 and herpes labialis. Alzheimers Rep 1998;1:173-178

78. Lin WR, Wozniak MA, Esiri MM, Klenerman P, Itzhaki RF. Herpes simplex encephalitis: involvement of apolipoprotein E genotype. J Neurol Neurosurg Psychiatry 2001; 70:117-119.

79. Rebeck GW, Kindy M, LaDu MJ. Apolipoprotein E and Alzheimer's disease: the protective effects of ApoE2 and E3. J Alzheimers Dis. 2002 Jun;4(3):145-54.

80. Fernandez-Miranda C, Aranda JL, Martin MA, Arenas J, Nunez V, Gomez de la Camara A. Apolipoprotein E polymorphism and carotid atherosclerosis in patients with coronary disease. Int J Cardiol. 2004 Apr; 94(2-3):209-12.

校內：2005-08-09公開
校外：2005-08-09公開

簡易檢索 / 詳目顯示

相關論文