There are three major types of human retroviruses, namely HIV, HTLV, and endogenous human retroviruses. This book presents the latest findings on the replication of these human retroviruses. This book is unique in that there has been no comparable book that integrates the findings from the three known classes of human retroviruses. Other books have focused on one of the three classes of human retroviruses individually. An accomplished international team of contributing authors have combined their expertise to provide cutting-edge findings in this important field. The book will be a valuable reference for students, researchers and medical professionals.
Author(s): Andrew M.L. Lever, Kuan-Teh Jeang, Ben Berkhout, Editors
Edition: 1
Publisher: World Scientific Publishing Company
Year: 2010
Language: English
Pages: 502
Tags: Биологические дисциплины;Микробиология и биотехнология;Вирусология;
Contents......Page 6
INTRODUCTION......Page 10
VIRAL INFECTION IN HP/HSCs......Page 11
RETROVIRUSES AND CANCER: SIGNIFICANCE OF INFECTION OF HEMATOPOIETIC PROGENITOR CELLS......Page 13
Avian Erythroblastosis Virus (AEV)......Page 14
Induction of erythroleukemia by Friend leukemia virus (FLV)......Page 15
Induction of T-Lymphoma by Moloney Murine Leukemia Virus......Page 19
Human Immunodeficiency Virus Type-1......Page 22
HIV infection of hematopoietic progenitor cells: In vivo and in vitro......Page 23
HIV-1-mediated hematosuppression: Role of viral protein gp120-env, Gag and Vpr......Page 26
Human T cell Leukemia Virus Type-1 and the Development of Adult T Cell Leukemia/Lymphoma (ATLL): Potential Role of Infectious Leukemic Stem Cells......Page 28
Tax1: The role of the HTLV-1 oncogene in ATL development......Page 29
Cell cycle arrest in HPCs: Dysregulation of p21cip1/waf1 (p21), p27kip1 (p27) and survivin......Page 30
REFERENCES......Page 34
INTRODUCTION......Page 56
Clonal Proliferation of HTLV-1-Infected Cells......Page 57
THE ONCOGENIC FUNCTIONS OF TAX......Page 58
Activation of the NF- κB pathway......Page 59
Activation of cyclin-dependent kinases (CDKs)......Page 61
Cellular Aneuploidy......Page 62
DNA Structural Damage......Page 63
Suppression of telomerase......Page 64
HBZ RNA AND PROTEIN IN LEUKEMOGENESIS......Page 65
p27Rex......Page 67
CONCLUDING REMARKS......Page 68
REFERENCES......Page 69
SUMMARY......Page 78
Protein Structure Studies......Page 79
Primary Structure Analysis......Page 80
Crystal Structure......Page 85
Solution Structure......Page 87
Transcription Assays......Page 90
Protein Localization......Page 91
Cell Adhesion Assay......Page 92
Analysis of Functional Products......Page 93
Two-Hybrid Analysis......Page 94
Immunoprecipitation......Page 96
Comprehensive Protein Complex Characterization Using Mass Spectrometry......Page 97
Antibody Arrays......Page 99
HLA Class I Peptide Profiling......Page 101
SERUM PROTEIN PROFILING......Page 102
FUTURE DIRECTIONS......Page 103
REFERENCES......Page 105
INTRODUCTION......Page 114
INITIAL STUDIES ON ANTISENSE TRANSCRIPTION IN RETROVIRUSES......Page 115
DISCOVERY OF HTLV-1 ANTISENSE TRANSCRIPTS......Page 118
REGULATION OF THE EXPRESSION OF HBZ......Page 120
CHARACTERIZATION OF THE VARIOUS ISOFORMS OF THE HTLV-1 HBZ PROTEIN AND CELLULAR LOCALIZATION......Page 123
STRUCTURE OF THE HBZ PROTEIN AND ITS INTERACTION PARTNERS......Page 125
FUNCTIONAL ASPECT OF HBZ IN RELATION TO REPLICATION OF HTLV-1......Page 127
THE IMPACT OF HBZ ON T-CELL PROLIFERATION AND TRANSFORMATION......Page 128
OTHER RETROVIRUSES AND ANTISENSE TRANSCRIPTION......Page 129
PERSPECTIVES......Page 131
REFERENCES......Page 132
SUMMARY......Page 138
INTRODUCTION......Page 139
Regulation of Basal Transcription by AP-1......Page 141
Regulation of Basal Transcription by Sp1/Sp3......Page 143
ACTIVATION OF HTLV-1 TRANSCRIPTION BY THE VIRAL PROTEIN TAX......Page 144
Tax Binds the A and C Domains of the vCRE......Page 145
Tax and CREB Recruit the Coactivators p300 and CBP to the HTLV-1 Promoter......Page 146
The Role of TORC/CRTC Coactivators in Tax-Dependent HTLV-1 Transcription......Page 148
The Role of Chromatin Remodeling Complexes at HTLV-1 Promoter......Page 150
Nucleosome-Displacement from the HTLV-1 Promoter......Page 151
Tax Recruits Methyltransferases to the Viral Promoter......Page 153
Tax Interacts with General Transcription Factors......Page 154
Tax Recruits the Elongation Factor, P-TEFb, to the Viral Promoter......Page 155
Transcription Originating from the 3' LTR......Page 156
Repression of HTLV-1 Transcription by Methylation of the Viral Promoter......Page 157
Repression of HTLV-1 Transcription by HDAC Complexes......Page 158
Repression of HTLV-1 Transcription by the Viral Protein HBZ......Page 160
Repression of HTLV-1 Transcription by Cellular bZIP Factors (C/EBP, ICER, ATFx)......Page 161
Negative Feedback Regulation of HTLV-1 Transcription by Tax......Page 163
REFERENCES......Page 164
SUMMARY......Page 180
INTRODUCTION......Page 181
HIV-1 and RNA Helicases......Page 185
HIV-1 and hnRNP Proteins......Page 190
HIV-1 and Sam68......Page 193
HIV-1 and Purα......Page 195
HIV-1 and Staufen......Page 196
HIV-1 and ABCE1......Page 197
HIV-1 Assembly and the Cytoskeleton......Page 198
HIV-1 AND siRNA LIBRARY SCREENS......Page 201
ANTIVIRALS TARGETING CELLULAR HOST FACTORS INVOLVED IN HIV-1 RNA METABOLISM......Page 202
ACKNOWLEDGMENTS......Page 204
REFERENCES......Page 205
INTRODUCTION......Page 220
GENOME-WIDE STUDIES OF RETROVIRAL INTEGRATION IN MAMMALIAN GENOMES......Page 222
Primary DNA Sequence......Page 225
General Genomic Features......Page 227
INTEGRATION PREFERENCES OF RETROVIRUSES AND RETROVIRAL VECTORS......Page 228
Moloney Murine Leukemia Virus (Mo-MLV)......Page 231
Human Immunodeficiency Virus Type 1 (HIV-1)......Page 232
Foamy Virus (FV)......Page 234
Human T-Cell Leukemia Virus Type 1 (HTLV-1)......Page 235
Ty Retrotransposons: A Paradigm for Tethered Integration......Page 236
Tethering Models for Retroviral Integration......Page 237
LEDGF/p75: A candidate for lentiviral integration tethering......Page 238
Transcription factors and gamma-retroviral integration tethering......Page 239
Tethering models for other retroviruses......Page 241
Integration-Site Selection and Viral Evolution......Page 242
Integration-Site Selection and Implications for Gene Therapy......Page 243
REFERENCES......Page 245
INTRODUCTION......Page 252
ENDOGENOUS RETROVIRUS GENE EXPRESSION IN PLACENTAS: DISCOVERY OF SYNCYTINS......Page 253
Human Placenta: Trophoblast Differentiation......Page 257
Syncytin-1......Page 259
Syncytin-2......Page 263
Syncytin-1 and syncytin-2 expression during in vitro trophoblast differentiation......Page 265
THE FUNCTIONS OF SYNCYTINS......Page 266
REGULATION OF SYNCYTIN EXPRESSION......Page 268
Preeclampsia......Page 270
Trisomy 21......Page 271
CONCLUSION......Page 272
REFERENCES......Page 273
SUMMARY......Page 280
INTRODUCTION......Page 281
CD4 DOWNREGULATION......Page 282
Vpu AND HIV-1 PARTICLE RELEASE......Page 283
THE PHENOTYPE OF Vpu-DEFECTIVE HIV-1 PARTICLE RELEASE......Page 285
TETHERIN......Page 287
MECHANISM OF Vpu’s ANTAGONISM OF TETHERIN......Page 291
SPECIES-SPECIFIC VARIANTS OF TETHERIN......Page 293
RESTRICTION OF OTHER ENVELOPED VIRUSES BY TETHERIN AND THEIR EVASION MECHANISMS......Page 295
ROLES OF Vpu AND TETHERIN IN THE PATHOGENESIS OF HIV/AIDS......Page 299
REFERENCES......Page 304
SUMMARY......Page 316
INTRODUCTION......Page 317
NUCLEOSIDE ANALOGS AS STRUCTURAL PROBES OF RT–SUBSTRATE INTERACTIONS......Page 319
Non-Hydrogen-Bonding Pyrimidine Isosteres......Page 320
Locked Nucleic Acid (LNA)......Page 322
Abasic Tetrahydrofuran Linkages......Page 323
Pyrrolo dC......Page 324
Examining HIV-1 RT Contacts with the Single-Stranded Template......Page 325
“Saturation” Nucleoside Analog Interference......Page 326
Protein/Nucleic Acid Complexes......Page 327
RT/RNase H Inhibitor Complexes......Page 329
Mass Spectrometric Footprinting of Nucleic Acids......Page 331
Active Site Mutagenesis......Page 334
Altering the “Steric Gate” of HIV-1 RT Induces 3TC Resistance......Page 335
Unnatural Amino Acid Mutagenesis of the RNase H Primer Grip......Page 336
Introducing Biophysical Probes into HIV-1 RT via Unnatural Amino Acids......Page 338
MEASURING INTERACTIONS OF HIV-1 RT WITH NUCLEIC ACID BY SINGLE-MOLECULE SPECTROSCOPY......Page 339
An Assay for Real-Time Observation of Dynamic RT:Substrate Interactions......Page 340
Sliding Dynamics of RT on Longer Substrates......Page 344
FUTURE PERSPECTIVES......Page 347
REFERENCES......Page 348
INTRODUCTION......Page 354
BIOLOGY OF HIV AND SIV......Page 357
NATURAL SIV INFECTION......Page 359
SHIV ANIMAL MODELS......Page 361
NON-HUMAN PRIMATES IN AIDS VACCINE DEVELOPMENT......Page 363
REFERENCES......Page 367
INTRODUCTION......Page 384
ON COFACTORS AND RESTRICTION FACTORS......Page 385
THE HIV-1 INTEGRASE PROTEIN AND INTEGRATION......Page 387
LENS EPITHELIUM DERIVED GROWTH FACTOR (LEDGF)/p75 TETHERS THE HIV-1 PRE-INTEGRATION COMPLEX TO THE CHROMOSOMES......Page 389
TRANSPORTIN-SR2 IMPORTS HIV-1 INTO THE NUCLEUS......Page 399
CONCLUSIONS......Page 402
REFERENCES......Page 404
INTRODUCTION......Page 416
APOBEC3G......Page 417
Retrovirus Restriction by DNA Cytidine Deamination......Page 418
Vif Neutralizes APOBEC3G Activity......Page 421
Evolutionary Perspective of the Mammalian APOBEC3 Family......Page 422
TRIM5......Page 424
Mechanism of Retrovirus Restriction by TRIM5 α......Page 427
TRIM5 Expression Profile......Page 430
Therapeutic Prospects for TRIM5......Page 431
Retrovirus Restriction by Particle Tethering......Page 432
Vpu Antagonizes BST2 Function......Page 433
Expression Profile of BST2......Page 435
Therapeutic Prospects for BST2......Page 436
REFERENCES......Page 437
SUMMARY......Page 448
INTRODUCTION......Page 449
DETERMINANTS OF REV-DEPENDENCE......Page 452
TRANSLATIONAL EFFECTS OF REV......Page 454
Limitations of Experimental Approaches for the Quantification of Rev-dependent Cytoplasmic RNA Levels......Page 455
Further Evidence for a Translational Effect of Rev......Page 457
Substitution of Rev by Heterologous Transport and Post-transcriptional Control Elements......Page 460
Cellular Proteins Modulating the Efficacy of Translation of Rev-Dependent RNAs......Page 462
MODULATION OF POST-TRANSLATIONAL EVENTS BY REV......Page 465
ENHANCEMENT OF RNA PACKAGING BY REV......Page 467
CONCLUDING REMARKS......Page 469
REFERENCES......Page 470
SUMMARY......Page 480
INTRODUCTION......Page 481
SMALL RNA-MEDIATED SILENCING IN MAMMALS......Page 484
HIV-1 GENOME ORGANIZATION AND REPLICATION......Page 485
HIV-1 INDUCED CHANGES IN CELLULAR miRNA EXPRESSION......Page 486
CELLULAR miRNAs TARGETING HIV-1......Page 487
miRNAs AND HIV-1 TROPISM......Page 488
TAT-MEDIATED RNAi SUPPRESSION......Page 489
HIV-1 ENCODED miRNAs......Page 490
HIV-1 AND TRBP......Page 491
RNAi-BASED HIV-1 THERAPEUTICS......Page 492
REFERENCES......Page 493
Index......Page 500
