HIV-1: Molecular Biology and Pathogenesis: Viral Mechanisms: Molecular Biology and Pathogenesis: Viral Mechanisms
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Table of contents
- Contentsvii
- Contributorsxiii
- Preface written by Robert C. Galloxvii
- Chapter 1: HIV-1 RNA Packaging1
- I. Chapter Overview1
- II. Introduction2
- III. The Packaging Pathway4
- IV. RNA/Protein Recognition for Encapsidation: Molecular and Structural Biology9
- V. Conclusions21
- References22
- Chapter 2: Structure and Function of the HIV Envelope Glycoprotein as Entry Mediator, Vaccine Immuno33
- I. Chapter Overview33
- II. Introduction34
- III. Structure of the Env (gp120-gp41)35
- IV. Env Interactions with CD4 and Coreceptor (CCR5 or CXCR4) Leading to Membrane Fusion45
- V. Env Interactions with Antibodies55
- VI. The Env as Vaccine Immunogen and Target for Inhibitors68
- VII. Conclusions79
- Acknowledgments79
- References79
- Chapter 3: HIV-1 Reverse Transcription: Close Encounters Between the Viral Genome and a Cellular tRN99
- I. Chapter Overview99
- II. Introduction100
- III. Reverse Transcription100
- IV. Specificity of tRNA Primer Usage104
- V. Identification of the PAS Motif114
- VI. Proposed Mechanism of Primer Activation116
- VII. HIV-1 Replication with a Nonself tRNA Primer Confirms the Importance of the PAS Motif119
- VIII. Conclusions125
- Acknowledgments127
- References127
- Chapter 4: Transcription of HIV: Tat and Cellular Chromatin137
- I. Chapter Overview137
- II. Introduction138
- III. Integrated HIV-1 LTR and Cellular Chromatin138
- IV. The HIV-1 Tat Protein and Its Modifications142
- V. Tat-Mediated Transactivation145
- V. Conclusions151
- Acknowledgments152
- References152
- Chapter 5: Posttranscriptional Control of HIV-1 and Other Retroviruses and Its Practical Application161
- I. Chapter Overview161
- II. Introduction162
- III. HIV-1 Regulation of Gene Expression165
- IV. Rev and Its Export Receptor CRM1167
- V. Posttranscriptional Regulation of Other Complex Retroviruses170
- VI. HIV-1 mRNAs Use Multiple Mechanisms to Express Many Proteins from One Transcript171
- VII. Rev-Dependence of HIV-1 mRNAs173
- VIII. Use of RNA Optimization to Achieve High Level of HIV-1 gag/pol and env Expression Plasmids175
- IX. Posttranscriptional Control of Simple Retroviruses177
- X. NXF1178
- XI. Cellular CTEs
- XII. Posttranscriptional Control of LTR-Retroelements
- XIII. Comparison of RNA Export Systems
- XIV. Replacement of Rev Regulation Leads to SIV Attenuation
- XV. Conclusions
- Acknowledgments183
- References183
- Chapter 6: HIV Accessory Genes Vif and Vpu199
- I. Chapter Overview
- II. Vif: A Potent Regulator of Viral Infectivity
- III. The HIV-1-Specific Vpu Protein
- References221
- Chapter 7: Interactions of HIV-1 Viral Protein R with Host Cell Proteins233
- I. Chapter Overview
- II. Introduction
- III. Effects of HIV-1 Vpr on Host Cellular Activities
- IV. Activation and Counteraction of Host Immune Responses by Vpr
- V. Development of Anti-Vpr Therapies
- Acknowledgment250
- References250
- Chapter 8: HIV-1 Protease: Structure, Dynamics, and Inhibition261
- I. Chapter Overview
- II. Introduction
- III. Mature Protease: Structure, Dynamics, and Relationship to Function
- IV. Active Site Inhibitors and Drug Resistance
- V. Dissociation of the Mature Protease Dimer and Characterization of the Monomeric Structure
- VI. Insights into the Structure of the Protease Precursor and Its Maturation
- Acknowledgments292
- References292
- Chapter 9: Properties, Functions, and Drug Targeting of the Multifunctional Nucleocapsid Protein of299
- I. Chapter Overview
- II. The NC Protein: The Story So Far
- III. The Structure of HIV-1 NC
- IV. The Network of NC Functions
- V. The Role of NC in HIV-1 Assembly
- VI. The Role of NC in HIV-1 Variability and Fitness
- VII. Anti-NC Drug Screening
- VIII. Conclusions and Future Prospects
- Acknowledgments
- References330
- Chapter 10: Human Immunodeficiency Virus Type 1 Assembly, Release, and Maturation347
- I. Chapter Overview347
- II. Overview of HIV-1 Assembly, Release, and Maturation348
- III. Multimerization of Gag to Form the Structural Framework of the Immature Virus Particle351
- IV. Encapsidation of the Viral RNA Genome356
- V. Trafficking Virion Components to the Site of Assembly358
- VI. Acquisition of a Lipid Bilayer and Associated Env Glycoproteins362
- VII. Virus Particle Release364
- VIII. Generating a Mature Infectious Virion368
- IX. HIV Assembly and Maturation as Targets for New Antiretroviral Drugs371
- Acknowledgments373
- References373
- Chapter 11: Role of Nef in HIV-1 Replication and Pathogenesis389
- I. Chapter Overview389
- II. Introduction390
- III. Nef and HIV-1 Infection of PBMCs392
- IV. Nef Studies in Human Thymic Systems393
- V. Mechanism of Nef Enhancement of Replication and Pathogenesis394
- VI. Conclusions401
- References402
- Chapter 12: Treatment Implications of the Latent Reservoir for HIV-1411
- I. Chapter Overview411
- II. Introduction412
- III. What is the Latent Reservoir?412
- IV. Resistance: Mechanism of Storage in the Latent Reservoir and Its Clinical Implications416
- V. Genotypic and Phenotypic Assays: Treatment Implications of the Latent Reservoir417
- VI. Drug Development: Taking the Latent Reservoir into Account418
- VII. Conclusions422
- References422
- Chapter 13: RNA Interference and HIV-1427
- I. Chapter Overview427
- II. Introduction428
- III. siRNA as Anti-HIV Therapy430
- IV. HIV-1 Remodels Cellular miRNA Expression in Infected Cells431
- V. Does HIV-1 Encode miRNAs?433
- VI. Future Perspectives434
- Acknowledgment435
- References436
- Index439
- Contents of Previous Volumes451
This volume covers the latest advances in the mechanisms of pathogenesis of the HIV-1 virus on target cells. Its companion volume, Advances in Pharmacology 56, shows how new developments in understanding the virus translate to the clinical setting.