Models of Protection Against HIV⁄SIV: Avoiding AIDS in Humans and Monkeys

Models of Protection Against HIV/SIV:Avoiding AIDS in humans and monkeys......Page 1
Copyright......Page 2
Contributors......Page 3
Foreword......Page 0
Models of Protection against HIV/SIV......Page 5
6 Host Genetics and Resistance to HIV-1 Infection......Page 7
Introduction......Page 8
Primate Lentiviral Infections in the Wild......Page 9
Natural History of Primate Lentiviruses......Page 10
Origin of HIV-1 and HIV-2......Page 13
Structural and Genetic Features of Primate Lentiviruses......Page 16
Barriers to Cross-Species Transmission: Virus Dependency Factors......Page 17
Barriers to Cross-Species Transmission: Host Restriction Factors......Page 18
Evasion and Antagonism of Antiretroviral Factors......Page 21
Development of HIV-1......Page 25
Possible Relevance of Vpu and Lack of Nef-Mediated Down-Modulation of TCR–CD3 for Viral Pathogenesis......Page 28
Why did Lentiviruses that do not Suppress T Cell Activation Emerge at all?......Page 33
Viral Coreceptor Tropism and Pathogenesis......Page 35
Latest Advances......Page 36
Summary and Perspectives......Page 37
References......Page 39
SIV Natural Hosts......Page 51
Seroprevalence of SIV in Natural Hosts and Modes of Transmission......Page 52
Evidence of Defective Virus......Page 256
Natural History of SIV Infection in Natural Hosts......Page 55
Primate Genome Comparison......Page 320
Cell Targets......Page 57
Viral Load......Page 59
Inflammation......Page 60
Dendritic Cells......Page 62
NKT Lymphocytes......Page 64
γδ T Cells......Page 65
SIV-Specific CD4+ T Cell Responses......Page 66
SIV-Specific CD8+ T Cell Responses......Page 67
B Cell Responses......Page 68
Hypotheses of Non-Pathogenicity......Page 70
Acknowledgements......Page 324
References......Page 72
3 Implications for Therapy......Page 84
Origins of HIV-2 Infection......Page 289
CD8+ T Cells......Page 86
Cross-Species Transmission and its Role in the Emergence of SIVs and HIVs......Page 89
Experimental Cross-Species Transmission of SIVs to Macaque Species and the Generation of the Animal Models for AIDS Research......Page 90
Animal Models......Page 91
Natural History of SIV Infection in Natural Hosts and Key Parameters that Have Potential Predictive Value to Assess Effective Therapeutic Interventions......Page 93
CD4 Expression in Natural Hosts......Page 94
CCR5 Expression in Natural Hosts......Page 95
Viral Replication......Page 96
CD4+ T Cell Dynamics During SIV Infection in Natural Hosts (Figure 3.3)......Page 98
Immune Activation/Inflammation and Bystander Apoptosis during Natural SIV Infections (Figure 3.3)......Page 100
Tregs (Regulatory T Cells) (Figure 3.3)......Page 101
Identification of Genetic Factors of Resistance to HIV-1 Infection by a Systems Biology Approach......Page 193
Dendritic Cells......Page 102
D......Page 103
IL-2......Page 104
IL-15......Page 105
IL-7......Page 106
Strategies to Reduce the Number of Target Cells......Page 107
Control of Microbial Translocation......Page 108
Strategies to Modulate T Regulatory Cells......Page 109
Strategies to Manipulate Dendritic Cells......Page 110
Strategies to Manipulate Th17 Cells......Page 112
Immune-Suppressive Drugs......Page 113
Mycophenolic Acid (MPA)......Page 114
Glucocorticoids......Page 115
Hydroxyurea......Page 116
Conclusions......Page 117
References......Page 118
Section II HIV-1-Exposed Seronegative Individuals......Page 136
Genesis of the Field......Page 137
Diversity of Cohorts......Page 138
Host Genetics......Page 139
Challenges to be Met......Page 141
References......Page 142
5 The Genital Mucosa, the Front Lines in the Defense Against HIV......Page 146
Introduction......Page 147
Sexual Exposure to HIV Infections in the Genital Mucosa......Page 148
Influence of Immune Factors in Genital Secretions on HIV Transmission......Page 149
Female Genital Secretions Mediate both Antiviral and Inflammatory Activity......Page 150
Host Genetics in HIV Vaccine Trials......Page 319
The Genital Epithelium Protects Against Viral Invasion by Multiple Mechanisms......Page 154
Expression of HIV-Binding Receptors in the Genital Mucosa......Page 156
Mucosal Humoral Immune Responses in HESN Individuals......Page 158
Adaptive Cellular Immune Responses in HESN Individuals......Page 160
Synthesis of a Model of Protection in HESN Individuals: The IQ Hypothesis......Page 161
Concluding Remarks......Page 162
References......Page 163
CCR5......Page 172
HLA and KIR......Page 174
Controversies in the Field......Page 175
Cytokines, Chemokines, Chemokine Receptors and Innate Antiviral Molecules......Page 177
Prospects for Future Studies of Host Genetic Factors Restricting HIV Infection......Page 179
The Pumwani Sex Worker Cohort......Page 180
HLA Class I and Class II Antigens and Resistance/Susceptibility to HIV-1 Infection......Page 182
Associations of HLA-A, -B, and -C Alleles, Allele Groups with Resistance and Susceptibility to HIV-1 Infection in the Pumwa .........Page 183
Associations of HLA Class II Antigens: DRB, DQA1, DQB1, DPA1 and DPB1 Alleles and Haplotypes with Resistance and Susceptibi .........Page 186
Additive Effect of HLA Associations with Resistance or Susceptibility to HIV-1 Infection......Page 189
Genetic Polymorphism of Trim5alpha and Resistance or Susceptibility to HIV-1 Infection......Page 190
Polymorphisms of Genes that Regulate Immune Response and Influence HIV-1 Infection Play an Important Role in the Resistance .........Page 192
Conclusion......Page 194
References......Page 195
Cell-Mediated Immunity......Page 211
C......Page 332
Quality of Response......Page 213
Differential CD8+ Epitope Specificity in HESNs......Page 214
HIV-Specific Responses in HESNs—Phenotype or Artifact?......Page 215
Marker of Exposure or Protective Mechanism?......Page 216
B......Page 217
Immune Quiescence or Immune Activation?......Page 218
Conclusion......Page 220
Section III HIV-1 Controllers......Page 230
Non-Progression to Infection......Page 231
The Identification of HIV Controllers......Page 232
Epidemiologic and Clinical Characteristics of HIV Controllers......Page 235
Mechanisms of Control and Open Questions......Page 240
References......Page 244
Conclusions......Page 251
Viral Factors of Elite Control......Page 252
Evidence of Replication-Competent Virus......Page 258
Elite Controllers have Plasma Levels of Viremia that are Similar to Patients on HAART......Page 259
Evidence of Viral Evolution in Elite Controllers......Page 260
Attenuated Plasma Virus; Cause or Effect of Elite Control?......Page 261
Clues from Transmission Pairs......Page 264
Clinical Implications......Page 265
References......Page 266
Introduction......Page 270
Immunodominance......Page 272
Polyfunctionality......Page 274
Proliferation......Page 275
CD4 T Cell Immune Responses......Page 276
Humoral Immune Responses......Page 278
Natural Killer Cells......Page 279
Conclusions......Page 280
References......Page 282
Epidemiology of HIV-2 Infection......Page 290
Natural History and Clinical Features of HIV-2 Infection......Page 291
Immune Activation and HIV-2 Pathogenesis......Page 293
Virological Aspects of HIV-2 Pathogenesis......Page 294
Immune Control in HIV-2 Infection......Page 296
Characteristics of HIV-Specific CD8+ T-Cells Associated with Viral Control......Page 298
Conclusions......Page 302
References......Page 303
IV Genetic Basis of Protection Against HIV......Page 312
Introduction......Page 313
Human Genetic Variation and HIV Control......Page 314
Clinical Implications......Page 322
Conclusions......Page 323
G......Page 333
H......Page 334
K......Page 335
S......Page 336
V......Page 338