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

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184 178. Lifson, J. D., M. B. Feinberg, G. R. Reyes, L. Rabin, B. Banapour, S. Chakrabarti, B. Moss, F. Wong-Staal, K. S. Steimer, and E. G. Engleman. 1986. Induction of CD4-dependent cell fusion by the HTLV- III/LAV envelope glycoprotein. Nature 323:725-8. 179. Lindenbach, B. D., M. J. Evans, A. J. Syder, B. Wolk, T. L. Tellinghuisen, C. C. Liu, T. Maruyama, R. O. Hynes, D. R. Burton, J. A. McKeating, and C. M. Rice. 2005. Complete replication of hepatitis C virus in cell culture. Science 309:623-6. 180. Lindenbach, B. D., P. Meuleman, A. Ploss, T. Vanwolleghem, A. J. Syder, J. A. McKeating, R. E. Lanford, S. M. Feinstone, M. E. Major, G. Leroux-Roels, and C. M. Rice. 2006. Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro. Proc Natl Acad Sci U S A 103:3805-9. 181. Lindenbach, B. D., and C. M. Rice. 2005. Unravelling hepatitis C virus replication from genome to function. Nature 436:933-8. 182. Logvinoff, C., M. E. Major, D. Oldach, S. Heyward, A. Talal, P. Balfe, S. M. Feinstone, H. Alter, C. M. Rice, and J. A. McKeating. 2004. Neutralizing antibody response during acute and chronic hepatitis C virus infection. Proc Natl Acad Sci U S A 101:10149-54. 183. Lohmann, V., F. Korner, J. Koch, U. Herian, L. Theilmann, and R. Bartenschlager. 1999. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 285:110-3. 184. Lopez, S., and C. F. Arias. 2004. Multistep entry of rotavirus into cells: a Versaillesque dance. Trends Microbiol 12:271-8. 185. Lozach, P. Y., A. Amara, B. Bartosch, J. L. Virelizier, F. Arenzana- Seisdedos, F. L. Cosset, and R. Altmeyer. 2004. C-type lectins L- SIGN and DC-SIGN capture and transmit infectious hepatitis C virus pseudotype particles. J Biol Chem 279:32035-45. 186. Lozach, P. Y., L. Burleigh, I. Staropoli, and A. Amara. 2007. The C type lectins DC-SIGN and L-SIGN: receptors for viral glycoproteins. Methods Mol Biol 379:51-68. 187. Lozach, P. Y., H. Lortat-Jacob, A. de Lacroix de Lavalette, I. Staropoli, S. Foung, A. Amara, C. Houles, F. Fieschi, O. Schwartz, J. L. Virelizier, F. Arenzana-Seisdedos, and R. Altmeyer. 2003. DC- SIGN and L-SIGN are high affinity binding receptors for hepatitis C virus glycoprotein E2. J Biol Chem 278:20358-66. 188. Ludwig, I. S., A. N. Lekkerkerker, E. Depla, F. Bosman, R. J. Musters, S. Depraetere, Y. van Kooyk, and T. B. Geijtenbeek. 2004. Hepatitis C virus targets DC-SIGN and L-SIGN to escape lysosomal degradation. J Virol 78:8322-32. 189. Ma, Y., J. Yates, Y. Liang, S. M. Lemon, and M. Yi. 2008. NS3 helicase domains involved in infectious intracellular hepatitis C virus particle assembly. J Virol 82:7624-39. 190. Maillard, P., T. Huby, U. Andreo, M. Moreau, J. Chapman, and A. Budkowska. 2006. The interaction of natural hepatitis C virus with human scavenger receptor SR-BI/Cla1 is mediated by ApoB-containing lipoproteins. Faseb J 20:735-7. 191. Major, M. E., K. Mihalik, M. Puig, B. Rehermann, M. Nascimbeni, C. M. Rice, and S. M. Feinstone. 2002. Previously infected and
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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
Page 143 and 144: 133 Figure 5-1 JFH-1 G451R has an a
Page 145 and 146: 135 Figure 5-2 CD81 dependence of J
Page 147 and 148: 137 G451R sE2 with hCD81 LEL we com
Page 149 and 150: 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: 183 hepatitis C virus envelope glyc
Page 197 and 198: 187 218. Monazahian, M., I. Bohme,
Page 199 and 200: 189 243. Perez-Berna, A. J., J. Gui
Page 201 and 202: 191 single-cycle production assay t
Page 203 and 204: 193 298. Strickland, G. T., S. S. E
Page 205 and 206: 195 Remaley, G. Csako, T. L. Eggerm
Page 207: 197 2007. Scavenger receptor class
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