HIV Interactions with Host Cell Proteins (eBook)

162085_1_En_FM1_OnlinePDF.pdf 1
162085_1_En_1_Chapter_OnlinePDF.pdf 10
Chapter : Host Restriction of HIV-1 by APOBEC3 and Viral Evasion Through Vif 10
Introduction 11
Non-Permissive Cells and the Identification of A3G 11
The APOBEC Family of Cytidine Deaminases 12
The Antiviral Mechanism of APOEBC3 Proteins: Deaminase Dependent 16
The Antiviral Mechanism of APOEBC3 Proteins: Deaminase Independent 17
A3G Structural Features 19
Packaging of APOBEC3 Molecules 20
Vif Targets APOBEC3 Proteins for Proteasome-Mediated Degradation 21
Vif May also Inhibit A3G by Degradation-Independent Mechanisms 23
Specificity of the Vif:APOBEC Interaction 24
Vif and Cell Cycle Inhibition 26
Other Roles for Vif 26
Conclusions 27
References 27
162085_1_En_2_Chapter_OnlinePDF.pdf 35
Chapter : Interactions of Viral protein U (Vpu) with Cellular Factors 35
Introduction 36
Expression 36
Comparative Genetics 36
mRNA 36
Subcellular Distribution 37
Structure 37
Transmembrane Domain 37
Cytoplasmic Domain 38
Function 38
Recruitment of an E3-Ubiquitin Ligase Complex to Membrane Proteins 38
CD4 39
BST-2/CD317 39
Interference with Degradation of Host Cell Proteins 39
Ikappabeta 40
beta-catenin 40
Ion Channel Activity 40
Delay in Protein Traffic Along the Biosynthetic Pathway 41
Enhancement of Virion-Release 41
Evasion of Adaptive Immunity 42
Downregulation of MHC-I 43
Downregulation of MHC-II 43
Upregulation of CD40 43
Interactions with Cellular Proteins 43
beta-TrCP 43
CD4 44
BST-2 44
CAML 47
Invariant Chain of MHC-II 47
UBP 48
TASK-1 48
Conclusion 48
Acknowledgements 49
References 49
162085_1_En_3_Chapter_OnlinePDF.pdf 54
Chapter : TRIM5alpha 54
Introduction 55
Postentry Restrictions 55
Fv1 55
Ref1 and Lv1 56
TRIM5a 57
Identification of TRIM5a Restriction 57
TRIM5a 57
TRIMCyp 60
Restriction Activity of TRIM5a 61
Interspecies Variation of TRIM5a and Retroviral Restriction 61
Role of TRIM5a Domains 62
How TRIM5a Works? 63
Inhibition of Normal Uncoating 63
Ubiquitin Ligase Activity of TRIM5a 64
Proteasome 64
TRIM5a Turnover 65
TRIM5a dynamics and trafficking 65
Cyclophilin A 66
Polymorphism 66
Conclusion 67
References 67
162085_1_En_4_Chapter_OnlinePDF.pdf 74
Chapter : Human Immunodeficiency Virus Type-1 Gag and Host Vesicular Trafficking Pathways 74
Introduction 75
Gag and Late Endosome Compartments/MVBs 76
Gag and ESCRT 78
Plasma Membrane-Specific Interactions: Lipid Raftsand PI(4,5)P2 80
Role of Adaptor Protein Complexes in HIV Assembly 81
GGAs, Arf Proteins, and Assembly 85
Role of Rab GTPases and Host Motor Proteins in HIV Assembly 85
Conclusions 87
References 88
162085_1_En_5_Chapter_OnlinePDF.pdf 92
Chapter : The Roles of Tetraspanins in HIV-1 Replication 92
Introduction 93
Tetraspanins: Organizers of Membrane-Based Processes 94
Structure and Subcellular Distribution of Tetraspanins 94
Cellular Functions of Tetraspanins 95
Tetraspanins are Regulators of HIV-1 Replication 96
Tetraspanins are present at viral exit sites 96
Tetraspanins in HIV-1 Virions Inhibit Env-Induced Membrane Fusion 98
Tetraspanins Regulate HIV-1 Entry and the Transcription of the Viral Genome in Newly Infected Cells 99
Tetraspanins Regulate Cell-to-Cell Transmission of HIV-1 100
How do Tetraspanins Regulate HIV-1 Entry, Viral Protein Expression, and Env/Receptor-Mediated Fusion Processes? 102
Tetraspanin Functions in Potential Target Cells and in Newly Infected Cells 102
Repression of Fusion Triggered by Virion-Associated or Producer Cell-Associated Env 103
Conclusions - Perspectives 103
References 104
162085_1_En_6_Chapter_OnlinePDF.pdf 110
Chapter : Imaging of HIV/Host Protein Interactions 110
Introduction 111
Techniques 111
Colocalization versus Interaction 112
Probing Association by Energy Transfer 114
FRET 114
BiFC 114
Improving Imaging Conditions by Increasing Sensitivity and Resolution 115
TIRF 117
PALM 118
Examples 119
Entry 119
Mobile Receptors 120
Hitching a Ride 120
Discriminating Entry from Endocytosis 121
Journey to the Center of the Nucleus 122
Exit 123
Correlative Imaging: The Best of Both Worlds 123
ESCRTing Through Microdomains 123
Shared Machinery 124
Dynamics of Budding VLPs 124
Superresolution Budding 125
Connecting Exit and Entry 126
Regulatory and Accessory Proteins 127
Tat 127
Nef Oligomerization 128
Conclusions 128
References 129
162085_1_En_7_Chapter_OnlinePDF.pdf 131
Chapter : Virological and Cellular Roles of the Transcriptional Coactivator LEDGF/p75 131
History and Nomenclature: Transcriptional Coactivator p75, LEDGF/p75, DFS70 132
Gene Organization and Splice Variants 133
Chromatin Binding 134
Interactions with Cellular and Viral Proteins 136
A Role in Transcriptional Regulation 137
Effects on Cell Survival 142
LEDGF/p75 and Autoimmunity 143
An Integration Cofactor for HIV-1 and Other Lentiviruses 143
LEDGF/p75 as a Therapeutic Target 146
References 146
162085_1_En_8_Chapter_OnlinePDF.pdf 153
Chapter : Implications of Nef: Host Cell Interactions in Viral Persistence and Progression to AIDS 153
Introduction 154
Interactions Facilitating Viral Immune Evasion 155
CD8+ T Cell Evasion: MHC-I Down-Modulation 155
NK Cell Evasion: Selective Down-Modulation of HLA-A and -B 157
Restricting MHC-II Antigen Presentation: Ii up-Modulation 158
Modulation of Signaling from the Cell Surface 159
Down-Modulation of TCR-CD3 159
Down-Modulation of the CD4 Receptor 160
Down-Modulation of Co-Stimulatory Molecules 161
CXCR4 Down-Modulation 162
Effects on the Immunological Synapse 162
Interactions Supporting SIV and HIV Replication 163
Enhancement of Virus Production 164
Subversion of T Cell Signaling Pathways 164
Activation of Viral and Cellular Transcription 166
CD4 Down-Modulation 166
Enhancement of Viral Transfer from DCs to T Cells 167
Enhancement of Virion Infectivity 167
Induction of Soluble Factors Facilitating Virus Spread 168
Effects of Nef on Programmed Cell Death 169
Interactions of Exogenous Nef with Host Cells 169
Conclusion 170
References 171
162085_1_En_9_Chapter_OnlinePDF.pdf 182
Chapter : Vpr and Its Interactions with Cellular Proteins 182
Introduction 183
Structure of Vpr 184
Interactions of Vpr with Cellular Proteins 185
Interactions of Vpr with the DNA Repair Machinery 185
Uracil DNA Glycosylase 185
The Human Homolog of S. cerevisiae Rad23 186
Vpr Induces a Signal That Resembles Genotoxic Stress 187
Interactions of Vpr with Cell Cycle Regulatory Elements 187
Vpr and 14-3-3 proteins 188
Vpr and ATR 189
Cdc25 189
Wee1 190
p21WAF 190
Sp1 190
p300 191
Vpr and the Ubiquitin/Proteasome System 191
Interactions of Vpr with the Apoptosis Machinery 193
Interactions of Vpr with Nuclear Pore and Nuclear Transport Elements 194
Vpr Binds to the Splicing Regulator, SAP145 195
Heat Shock Protein 70 196
Cyclophilin A 196
The Glucocorticoid Receptor 196
Vpx as a Paralog of Vpr 197
Conclusions and Future Directions 198
References 198
162085_1_En_BM2_OnlinePDF.pdf 206
: Index 206