Viruses, Genes, and Cancer (Current Topics in Microbiology and Immunology, 407)

This volume focuses on virus-host cell interactions, cellular genes acquired or modulated by viruses, the pathological effects of these interactions, and therapeutic interventions. Several chapters specifically address the role of viruses and genes – such as oncogenes, proto-oncogenes, or tumor suppressor genes – in the etiology of human cancer. Oncogenic signaling by PI3 kinase, mTOR, Akt, or the major cancer drivers MYC and RAF, and the role of tumor suppressors like p53, are discussed in detail. The volume also explores the emerging role of noncoding RNAs such as microRNAs in tumorigenesis and cancer therapeutics, and offers new insights into the role of HIV-host interactions relevant to pathogenesis and treatment. Gathering contributions written by leading scientists in their respective fields, the volume offers a valuable resource for researchers and clinicians alike. Read more... Abstract: This volume focuses on virus-host cell interactions, cellular genes acquired or modulated by viruses, the pathological effects of these interactions, and therapeutic interventions. Read more... Preface 6 A Brief Homage to Peter Vogt 10 Contents 14 21 Exchange of Genetic Sequences Between Viruses and Hosts 15 Abstract 15 1 A Year of Virological Anniversaries 16 1.1 Bacteriophage and Prokaryote Transduction 17 1.2 The Debt of Tumor Virus Research to Phage Genetics 18 1.3 Fifty-Five Years of Peter Vogt’s Contributions to Retroviruses and Oncogenes 19 2 Acquisition of Host Genes by Viruses 20 2.1 Oncogenesis by Simple Retroviruses and Transduction of Oncogenes 20 2.2 Why Is Retroviral Transduction not a Major Driver of Virus or Host Evolution? 21 2.3 Incorporation of Host Genetic Sequences into Complex Viruses 22 3 Acquisition of Viral Genes by Hosts 24 3.1 Viral Genomes in Host DNA: Retroviruses, DNA Viruses and RNA Viruses 24 3.2 Evolutionary Dynamics of Exogenous and Endogenous Retroviruses 26 3.3 Pathogenic and Beneficial Attributes of Endogenous Retroviruses 28 3.4 Role of Endogenous Retroviral Envelopes in the Placenta 29 4 Endosymbiont Organelles in Eukaryotic Cells and Their Horizontal Transfer in Cancer 31 4.1 Evolution of Complex Cells and Their Organelles 31 4.2 Horizontal Spread of Cancer Cells 32 4.3 Colonization of Cancer Cells by Host Mitochondria 33 5 Concluding Remarks 34 Acknowledgements 34 References 34 33 Virus-Host Gene Interactions Define HIV-1 Disease Progression 44 Abstract 44 1 Introduction 45 2 HIV-1 Transmission 45 3 Current Concepts of Genital Tract Infection and Systemic Spread 46 4 HIV-1 Transmission is Linked to a Genetic Bottleneck 47 5 Evidence for Both Chance and Selection Influencing Transmission 51 6 Properties of the Transmitted/Founder Virus 54 7 A Complex Interplay Between Host Immunity and Transmitted Virus Phenotype Defines Viral Control and Disease Progression 58 8 Conclusions 63 References 64 35 Sequencing the Biology of Entry: The Retroviral env Gene 77 Abstract 77 1 Introduction 78 2 Avian Leukosis Virus (ALV) 80 2.1 History of Viruses and Susceptibility 81 2.2 The Viral Env Gene/Protein 82 2.3 Sequencing, Cloning, and Sequencing 82 2.4 Receptors 83 2.5 Subgroup J, Biology in Real Time 84 3 HIV-1 Env Proteins: Still Trying to Get It Right 84 3.1 The Two Evolutionary Variants of R5 T Cell-Tropic Viruses 86 3.2 A Fourth Entry Phenotype Is an Artifact of Tissue Culture Adaptation 88 Acknowledgements 89 References 89 3 Infectious Agents in Bovine Red Meat and Milk and Their Potential Role in Cancer and Other Chronic Diseases 95 Abstract 95 1 Increased Cancer Risk After Red Meat or Dairy Product Consumption 96 2 Risk Reduction for Specific Cancers and Two Chronic Diseases by Long-Time Breast-Feeding 98 3 Are Diet-Attributed Factors Increasing Cancer Risks Human-Specific? 100 4 Increased Risk for Neurodegenerative Diseases After Red Meat or Dairy Product Consumption 101 5 Increased Risk for Cardiovascular or Autoimmune Diseases After Red Meat or Dairy Product Consumption 102 6 Are the Observed Effects for Meat and Dairy Product Consumption Species-Specific for Eurasian Bos Taurus-Derived Dairy Cattle? 104 7 Evidence for Episomally Persisting Infectious Factors Transmissible from Dairy Cattle to Humans 105 8 Synergistic Model for Interactions of These Infections with Other Viral Infections and Genetic or Epigenetic Modifications 110 8.1 Multiple Sclerosis 110 8.2 Solid Cancers 113 8.3 Cross-reactivity of BMMF Antibodies with Those of Neu5Gc? 114 9 Conclusions 117 Acknowledgements 118 References 118 4 MYC and RAF: Key Effectors in Cellular Signaling and Major Drivers in Human Cancer 129 Abstract 129 1 Introduction 130 2 Protein Structure 132 2.1 MYC Proteins 132 2.2 RAF Proteins 134 3 Cellular Signaling 136 3.1 The MYC Master Regulator 138 3.2 The RAF Signaling Node 141 4 Tumorigenesis 143 4.1 Cancer Driver MYC 143 4.2 Oncogenic RAF Signaling 145 5 Pharmacological Interference 147 5.1 MYC Inhibition 147 5.2 RAF Inhibition 150 6 Conclusions 151 Acknowledgements 152 References 152 6 Oncogenic Roles of the PI3K/AKT/mTOR Axis 164 Abstract 164 1 Introduction 165 2 Overview of the PI3K/AKT/MTOR Signaling Pathway 166 2.1 PI3Ks and PI3K-Associated Phosphatases 166 2.2 PTEN and INPP4B 167 2.3 AKT 168 2.4 mTOR 168 3 Oncoproteins of the PI3K/AKT/MTOR Signaling Axis 169 3.1 PI3K 169 3.1.1 p110α 169 3.1.2 Other Isoforms of PI3Ks 176 3.2 AKT 177 3.3 mTOR and RHEB 179 3.4 eIF4E 181 4 Negative Regulators of the PI3K/AKT Axis in Oncogenic Transformation 182 4.1 PTEN 182 4.2 INPP4B 183 4.3 PIPP 183 4.4 PHLPP1 184 4.5 TSC1 and TSC2 184 4.6 LKB1 184 5 Mechanisms of Oncogenic Transformation by the PI3K/AKT/mTORC1 Signaling 185 5.1 Cell Proliferation and Survival 185 5.2 Metabolic Reprogramming 186 5.3 Suppressing Autophagy and Senescence 187 5.4 Invasion/Metastasis, EMT 188 6 Conclusions 188 Acknowledgments 189 References 189 34 MicroRNA Dysregulation to Identify Novel Therapeutic Targets 201 Abstract 201 1 Introduction 202 1.1 A Long Journey 202 2 Burkitt Lymphoma 202 3 Follicular Lymphoma 204 4 Chronic Lymphocytic Leukemia 206 5 miR-15a and miR-16-1 Are Deleted in CLL 208 6 Interaction of Venetoclax with BCL2 210 References 211 5 The Evolution of Tumor Formation in Humans and Mice with Inherited Mutations in the p53 Gene 214 Abstract 214 1 Background 215 2 The Li-Fraumeni Syndrome 217 3 Li-Fraumeni Syndrome in Mice 222 4 Quantitation of the Clonal Evolution of Thymic Lymphomas in Mice with Mutant p53 Proteins 224 5 Conclusions 226 Acknowledgements 228 References 228 Front Matter ....Pages i-xiii Exchange of Genetic Sequences Between Viruses and Hosts (Robin A. Weiss)....Pages 1-29 Virus-Host Gene Interactions Define HIV-1 Disease Progression (Daniela C. Monaco, Zachary Ende, Eric Hunter)....Pages 31-63 Sequencing the Biology of Entry: The Retroviral env Gene (Ronald Swanstrom, William D. Graham, Shuntai Zhou)....Pages 65-82 Infectious Agents in Bovine Red Meat and Milk and Their Potential Role in Cancer and Other Chronic Diseases (Harald zur Hausen, Timo Bund, Ethel-Michele de Villiers)....Pages 83-116 MYC and RAF: Key Effectors in Cellular Signaling and Major Drivers in Human Cancer (Eduard Stefan, Klaus Bister)....Pages 117-151 Oncogenic Roles of the PI3K/AKT/mTOR Axis (Masahiro Aoki, Teruaki Fujishita)....Pages 153-189 MicroRNA Dysregulation to Identify Novel Therapeutic Targets (Carlo M. Croce)....Pages 191-203 The Evolution of Tumor Formation in Humans and Mice with Inherited Mutations in the p53 Gene (Arnold J Levine)....Pages 205-221 "This volume focuses on virus-host cell interactions, cellular genes acquired or modulated by viruses, the pathological effects of these interactions, and therapeutic interventions. Several chapters specifically address the role of viruses and genes {u2013} such as oncogenes, proto-oncogenes, or tumor suppressor genes {u2013} in the etiology of human cancer. Oncogenic signaling by PI3 kinase, mTOR, Akt, or the major cancer drivers MYC and RAF, and the role of tumor suppressors like p53, are discussed in detail. The volume also explores the emerging role of noncoding RNAs such as microRNAs in tumorigenesis and cancer therapeutics, and offers new insights into the role of HIV-host interactions relevant to pathogenesis and treatment. Gathering contributions written by leading scientists in their respective fields, the volume offers a valuable resource for researchers and clinicians alike."--Publisher's description