The role of scavenger receptor BI in hepatitis - eTheses Repository ...

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192 283. Shoukry, N. H., A. Grakoui, M. Houghton, D. Y. Chien, J. Ghrayeb, K. A. Reimann, and C. M. Walker. 2003. Memory CD8+ T cells are required for protection from persistent hepatitis C virus infection. J Exp Med 197:1645-55. 284. Silva, M. C., J. Schroer, and T. Shenk. 2005. Human cytomegalovirus cell-to-cell spread in the absence of an essential assembly protein. Proc Natl Acad Sci U S A 102:2081-6. 285. Silver, D. L. 2002. A carboxyl-terminal PDZ-interacting domain of scavenger receptor B, type I is essential for cell surface expression in liver. J Biol Chem 277:34042-7. 286. Silver, D. L. 2004. SR-BI and Protein-Protein Interactions in Hepatic High Density Lipoproteins Metabolism. Reviews in Endocrine & Metabolic Disorders 5:327-333. 287. Silver, D. L., N. Wang, X. Xiao, and A. R. Tall. 2001. High density lipoprotein (HDL) particle uptake mediated by scavenger receptor class B type 1 results in selective sorting of HDL cholesterol from protein and polarized cholesterol secretion. J Biol Chem 276:25287-93. 288. Silvie, O., S. Charrin, M. Billard, J. F. Franetich, K. L. Clark, G. J. van Gemert, R. W. Sauerwein, F. Dautry, C. Boucheix, D. Mazier, and E. Rubinstein. 2006. Cholesterol contributes to the organization of tetraspanin-enriched microdomains and to CD81-dependent infection by malaria sporozoites. J Cell Sci 119:1992-2002. 289. Simmonds, P. 2004. Genetic diversity and evolution of hepatitis C virus--15 years on. J Gen Virol 85:3173-88. 290. Simmonds, P., E. C. Holmes, T. A. Cha, S. W. Chan, F. McOmish, B. Irvine, E. Beall, P. L. Yap, J. Kolberg, and M. S. Urdea. 1993. Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region. J Gen Virol 74 :2391-9. 291. Smith, A. E., and A. Helenius. 2004. How viruses enter animal cells. Science 304:237-42. 292. Smith, D. B. 1999. Evolution of the hypervariable region of hepatitis C virus. J Viral Hepat 6 Suppl 1:41-6. 293. Spear, P. G., S. Manoj, M. Yoon, C. R. Jogger, A. Zago, and D. Myscofski. 2006. Different receptors binding to distinct interfaces on herpes simplex virus gD can trigger events leading to cell fusion and viral entry. Virology 344:17-24. 294. Stamataki, Z., C. Shannon-Lowe, J. Shaw, D. Mutimer, A. Rickinson, J. Gordon, D.H. Adams, P. Balfe and J.A. McKeating. 2008. Hepatitis C virus association with peripheral blood B lymphocytes potentiates viral infection of liver derived hepatoma cells. Blood 113:585-93 295. Stamataki, Z., J. Grove, P. Balfe, and J. A. McKeating. 2008. Hepatitis C virus entry and neutralization. Clin Liver Dis 12:693-712. 296. Steinmann, E., F. Penin, S. Kallis, A. H. Patel, R. Bartenschlager, and T. Pietschmann. 2007. Hepatitis C virus p7 protein is crucial for assembly and release of infectious virions. PLoS Pathog 3:e103. 297. StGelais, C., T. J. Tuthill, D. S. Clarke, D. J. Rowlands, M. Harris, and S. Griffin. 2007. Inhibition of hepatitis C virus p7 membrane channels in a liposome-based assay system. Antiviral Res 76:48-58.
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Page 1 and 2:
The role of scavenger receptor B-I
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i Abstract. With 170 million infect
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iii Acknowledgements. I would like
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v 5 Results: Identification of a re
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vii Figure 5-5 Analysis of JFH-1 wt
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1 Introduction 1.1 The disease. 1 D
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3 predominantly immuno-pathogenic i
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5 Aside from considerations of the
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7 Current attempts to design a HCV
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1.2 An elusive pathogen. 9 The emer
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11 PCR). This technique is highly s
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13 Within six years of the descript
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1.3 Basic virology. 15 Like other m
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17 Figure 1-2 HCV genome and polypr
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19 241). E1 and E2 are anchored to
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21 The characterisation of HCV geno
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23 in the E1 and E2 glycoprotein ge
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25 The solution reached by a great
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27 binding to mouse cells. sE2 inte
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29 density lipoprotein (HDL), allow
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31 blood brain barrier is permeable
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33 act as receptors for viral entry
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1.4.2 Attachment factors 35 The tru
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1.4.3 Endocytosis and fusion 37 Aft
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39 1.4.4 Co-receptor interplay and
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41 inhibition of protein kinase A (
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1.5 Lipoproteins 43 Since 1992 ther
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45 Lipoproteins exist in a dynamic
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47 and delivers its cargo via the w
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49 uptake of cholesterol from LDL (
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Figure 1-4 SR-BI-lipoprotein intera
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53 In summary the class B scavenger
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55 In 1992 Thomssen et. al. demonst
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57 lipoprotein association promotes
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59 Figure 1-5 Lipo-viro-particle as
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61 In vitro culture medium, into wh
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2 Materials and methods. 2.1 Cell l
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Preparation of rat anti-E2 mAbs. 65
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2.4 Basic techniques. Flow cytometr
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69 6. Finally, the cells were washe
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71 (Promega, WI, USA) kits accordin
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73 proteins and are incapable of fu
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75 spectrophotometer (Amersham), we
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77 Figure 2-2 Electroporated Huh-7.
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79 5. Data is expressed as percenta
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81 (Invitrogen). The samples to be
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83 1. The SR-BII coding region was
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2.7 Cloning and synthesis of JFH-1
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The sequence encoding amino acids 3
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Figure 2-6 sE2 sequencing. 89 JFH-1
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91 7. Large scale transfections wer
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93 3 Results: Investigations using
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95 3.2 CHO cells expressing human S
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Figure 3-3 Ability of anti-E2 mAb t
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99 3.3 The interaction of sE2 with
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101 Figure 3-5 Position of SR-BI mu
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103 Table 3-2 Investigation of cell
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105 3.4 Expression of SR-BII in CHO
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3.5 Discussion. 107 We have demonst
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109 may offer a tool to study the i
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111 Figure 4-1A displays endogenous
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113 4.2 Exogenous expression of SR-
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115 4.3 Evidence of enhanced JFH-1
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117 4.4 SR-BI expression levels lim
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119 4.5 Murine SR-BI does not enhan
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121 4.6 SR-BI/II expression levels
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123 Figure 4-5 Over expression of S
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125 Figure 4-6 Anti-SR-BI serum inh
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127 Figure 4-7 Infection of Huh-7.5
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129 cells is largely manifested in
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131 5 Results: Identification of a
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133 Figure 5-1 JFH-1 G451R has an a
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135 Figure 5-2 CD81 dependence of J
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137 G451R sE2 with hCD81 LEL we com
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139 Figure 5-4 JFH-1 wt and G451R s
Page 151 and 152: 141 demonstrated a lower dependence
Page 153 and 154: 143 Figure 5-6 Relationship between
Page 155 and 156: 145 flow cytometry (data not shown)
Page 157 and 158: 147 5.6 Low density JFH-1 particles
Page 159 and 160: 5.7 Discussion. 149 We have demonst
Page 161 and 162: 151 Numerous reports have used dens
Page 163 and 164: 153 demonstrate that low density JF
Page 165 and 166: 155 to over express SR-BI we were a
Page 167 and 168: 157 5-1), better able to engage CD8
Page 169 and 170: 159 Figure 6-1 An overview of antib
Page 171 and 172: 161 it is believed that ligation of
Page 173 and 174: 163 Given our and other’s finding
Page 175 and 176: 6.3 HCV lipo-viro-particles. 165 As
Page 177 and 178: 167 represent the hyper-variable re
Page 179 and 180: 169 The G451R mutation disrupts the
Page 181 and 182: 7 Bibliography 171 1. Acton, S., D.
Page 183 and 184: 173 include the CD81 tetraspanin an
Page 185 and 186: 175 receptor class B type I and inh
Page 187 and 188: 177 83. Drummer, H. E., K. A. Wilso
Page 189 and 190: 179 KewalRamani, D. R. Littman, C.
Page 191 and 192: 181 King. 1996. Efficient infection
Page 193 and 194: 183 hepatitis C virus envelope glyc
Page 195 and 196: 185 recovered chimpanzees exhibit r
Page 197 and 198: 187 218. Monazahian, M., I. Bohme,
Page 199 and 200: 189 243. Perez-Berna, A. J., J. Gui
Page 201: 191 single-cycle production assay t
Page 205 and 206: 195 Remaley, G. Csako, T. L. Eggerm
Page 207: 197 2007. Scavenger receptor class
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