HIV: Molecular Biology and Pathogenesis: Viral Mechanisms: Molecular Biology and Pathogenesis: Viral Mechanisms
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Table of contents
- Contentsv
- Contributorsxiii
- Prefacexvii
- Chapter 1. HIV RNA Packaging and Lentivirus-Based Vectors1
- I. Introduction1
- II. HIV RNA Packaging2
- III. Summary21
- References22
- Chapter 2. Multiple Biological Roles Associated with the Repeat (R) Region of the HIV-1 RNA Genome29
- I. Introduction29
- II. Transcription34
- III. Polyadenylation37
- IV. mRNA Translation48
- V. RNA Dimerization/Packaging49
- VI. Reverse Transcription51
- VII. Perspective and Future Directions61
- References63
- Chapter 3. HIV Accessory Proteins: Multifunctional Components of a Complex System75
- I. Introduction75
- II. Vif: A Potent Regulator of Viral Infectivity77
- III. Functional Domains in Vif78
- IV. Vif Associates with the Cytoskeleton80
- V. Vif as a Possible Regulator of Gag/Pol Polyprotein Processing81
- VI. Virion-Associated Vif May Have a Crucial Role in Regulating Viral Infectivity81
- VII. Vpr and Vpx83
- VIII. Vpr as a Transcriptional Activator85
- IX. Vpr as a Coactivator of the Glucocorticoid Receptor85
- X. Vpr-Induced Cell-Cycle Arrest86
- XI. Nuclear Import87
- XII. The Multifunctional Nef Protein88
- XIII. Downregulation of Cell-Surface CD489
- XIV. Downregulation of MHC Class I94
- XV. Enhancement of Viral Infectivity95
- XVI. Acceleration of Disease Progression96
- XVII. HIV-1-Specific Vpu Protein99
- XVIII. Vpu-Mediated CD4 Degradation99
- XIX. Enhancement of Viral Particle Release103
- References104
- Chapter 4. Role of Chromatin in HIV-1 Transcriptional Regulation121
- I. Introduction121
- II. HIV-1 Transcriptional Regulatory Elements122
- III. Chromatin Is an Integral Component of the Transcriptional Regulatory Apparatus125
- IV. HIV-1 Retroviral Integration and Chromatin128
- V. DNase I-Hypersensitive Sites in the HIV-1 Genome130
- VI. Nucleosomes Are Precisely Positioned in the 5 LTR131
- VII. Disruption of a Single Nucleosome at the Transcription Start Site during HIV-1 Transcriptional133
- VIII. Two Novel Regulatory Regions Are Associated with DNase I-Hypersensitive Sites in the HIV-1 Pro136
- IX. Role of Histone Acetylation/Deacetylation in HIV-1 Transcriptional Regulation141
- X. Role of Tat in HIV-1 Promoter Chromatin Remodeling and Transcriptional Activation143
- XI. Study of HIV-1 Transcription using in vitro Chromatin- Reconstituted Templates146
- XII. Conclusions148
- References150
- Chapter 5. NF-κB and HIV: Linking Viral and Immune Activation161
- I. Introduction161
- II. Historical Perspectives162
- III. The NF-κB/Rel Transcription Factors163
- IV. NF-κB and the Regulation of HIV Transcription171
- V. Other Roles for NF-κB in HIV Infection180
- VI. NF-κB and HIV Replication182
- VII. NF-κB and HIV Pathogenesis187
- VIII. Therapeutic Modulation of NF-κB: A Role in HIV Therapy?191
- IX. Conclusions194
- References195
- Chapter 6. Tat as a Transcriptional Activator and a Potential Therapeutic Target for HIV-1209
- I. Mechanisms of Tat-Mediated Trans-Activation209
- II. Cellular Cofactors for Trans-Activation212
- III. Therapeutic Anti-Tat Strategies217
- References219
- Chapter 7. From the Outside In: Extracellular Activities of HIV Tat229
- I. Introduction229
- II. Tat and Angiogenesis„The Kaposi Connection233
- III. Tat and Immunosuppression237
- IV. Tat as a Cytokine240
- References243
- Chapter 8. Rev Protein and Its Cellular Partners251
- I. Introduction251
- II. Characteristics of the Rev Protein255
- III. Rev and Nuclear Export Factors260
- IV. Rev and Nuclear Import Factors274
- V. Rev and RNA Splicing Factors277
- VI. Rev Targeted Therapy279
- VIII. Concluding Remarks283
- References283
- Chapter 9. HIV-1 Nef: A Critical Factor in Viral-Induced Pathogenesis299
- I. Introduction299
- II. Historical Background of Nef Involvement in Pathogenesis301
- III. Nef Structure303
- IV. Nef Function(s)309
- V. Conclusions and Discussion331
- References332
- Chapter 10. Nucleocapsid Protein of Human Immunodeficiency Virus as a Model Protein with Chaperoning345
- I. The Nucleocore345
- II. Nucleic Acid Chaperoning Activities of Nucleocapsid Protein350
- III. Nucleocapsid Protein and Virion Core Assembly354
- IV. Phylogenic Relationships between HIV-1 NCp7 and Nucleocapsid Protein of Other Retroviruses357
- V. NCp7 as a Target for Anti-HIV Inhibitors361
- VI. Future Prospects363
- References364
- Chapter 11. Bioactive CD4 Ligands as Pre- and/or Postbinding Inhibitors of HIV-1373
- I. Introducing the CD4 Molecule373
- II. Ligands of CD4376
- III. Dissection of CD4 Structure–Function Relationship by Mean of Antibodies and Synthetic Peptide381
- IV. Which Conclusions Can Be Drawn about the Function of CDR3-Loop Ligands?391
- V. Trials of Anti-CD4 mAbs for Treatment of HIV-Infected Patients395
- VI. Trials of CD4-Interacting Peptides in Human Therapy396
- VII. Future Developments of CDR3-Loop Ligands397
- References397
- Chapter 12. Coreceptors for Human Immunodeficiency Virus and Simian Immunode.ciency Virus409
- I. Introduction409
- II. Cellular Tropism of HIV and SIV410
- III. A History of HIV Receptors412
- IV. Assays for Coreceptor Activity413
- V. Comparison of the Different Assays for Coreceptor Activity418
- VI. Discovery of Additional Coreceptors (1996 to 1999)419
- VII. Coreceptor Use for HIV-1, HIV-2, and SIV424
- VIII. Summary of Coreceptor Use for HIV-1, HIV-2, and SIV435
- IX. Expression and Activity of Coreceptors in Cells and Tissues440
- X. Can Coreceptor Use Always Explain Tropism?447
- XI. Envelope Interactions with CD4 and Coreceptor448
- XII. Coreceptors and Pathogenesis449
- XIII. Possible Roles for Alternative Coreceptors451
- XIV. Some Remaining Questions Regarding Coreceptor Use454
- XV. Concluding Remarks455
- References457
- Index479
- Contents of Previous Volumes491
The cumulative death toll from AIDS has reached 16.3 million individuals, and more than 33 million persons are currently living with HIV-1. Although it is one of the most-widely studied viruses, many mysteries remain about this pathogen. In this comprehensive two-volume set, HIV-1: Molecular Biology and Pathogenesis, leading investigators in HIV research present a timely picture of the molecular mechanisms which guide HIV-1 expression and replication and provide the most current clinical strategies for combating this virus. Twenty-six teams of experts unravel structure-function interactions of HIV-1 with host cells and the resulting pathological consequences, review strategies fo treatment, and describe ongoing progress in developing animal models and prophylactic vaccines.
The two volumes, covering viral mechanisms and clinical applications, respectively, are written by an international collection of AIDS expers from North America, Europe, Australia, and Asia.
Key Features
* Detailed insights into viral packaging, expression, and assembly
* Mechanistic understanding of how HIV interacts with receptors and infects cells
* Delineation of virally encoded regulatory processes unique to HIV
* Clinical Applications:
* An updated review of current chemotherapeutics for HIV
* New concepts in the discovery and design of novel anti-HIV drugs
* The latest developments in HIV-vaccine research
The two volumes, covering viral mechanisms and clinical applications, respectively, are written by an international collection of AIDS expers from North America, Europe, Australia, and Asia.
Key Features
* Detailed insights into viral packaging, expression, and assembly
* Mechanistic understanding of how HIV interacts with receptors and infects cells
* Delineation of virally encoded regulatory processes unique to HIV
* Clinical Applications:
* An updated review of current chemotherapeutics for HIV
* New concepts in the discovery and design of novel anti-HIV drugs
* The latest developments in HIV-vaccine research