Contents

Introduction ...... xi

María-Carla SALEH and Félix AUGUSTO REY

Chapter 1. DNA ...... 1

Lindsey M. COSTANTINI and Blossom DAMANIA 1.1. Introduction to DNA viruses ...... 1 1.1.1. What are the most abundant DNA viruses? ...... 2 1.1.2. Human DNA viruses ...... 4 1.2. Taxonomy and structure ...... 6 1.2.1. Small DNA tumor , e.g. human papillomavirus ...... 7 1.2.2. Large DNA tumor virus, e.g. Kaposi’s sarcoma-associated herpesvirus ...... 7 1.3. Genomes ...... 8 1.3.1. HPV, a small DNA tumor virus genome ...... 9 1.3.2. KSHV, a large DNA tumor virus genome ...... 10 1.4. Gene expression and regulation ...... 10 1.4.1. Small DNA tumor virus gene expression, the HPV example .... 12 1.4.2. LargeCOPYRIGHTED DNA tumor virus gene expression, MATERIAL the KSHV example ... 13 1.4.3. DNA virus inhibition of cellular gene expression ...... 14 1.5. Infectious cycle ...... 15 1.5.1. Small DNA tumor virus life cycle, the HPV example ...... 16 1.5.2. Large DNA tumor virus life cycle, the KSHV example ...... 18

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1.6. Viral-induced cellular survival ...... 20 1.6.1. Small DNA tumor virus enhancement of cell survival, e.g. HPV ...... 21 1.6.2. Large DNA tumor virus enhancement of cell survival, e.g. KSHV ...... 21 1.7. Disease prevalence and prevention ...... 22 1.7.1. HPV, a small tumor DNA virus and disease associations ...... 22 1.7.2. KSHV, a large DNA tumor virus and disease associations ..... 24 1.8. Conclusion ...... 25 1.9. References ...... 26

Chapter 2. Double-stranded RNA Viruses ...... 33

Michelle M. ARNOLD, Albie VAN DIJK and Susana LÓPEZ 2.1. Introduction ...... 33 2.2. ...... 37 2.2.1. Virion structure ...... 37 2.2.2. Genome ...... 38 2.2.3. Virus entry ...... 39 2.2.4. Transcription, replication and genome segment sorting ...... 40 2.2.5. Host cell interactions: protein synthesis ...... 41 2.2.6. Innate immune evasion ...... 42 2.3. Reoviruses ...... 43 2.3.1. The use of reovirus as an anti-cancer agent...... 43 2.3.2. Virion structure ...... 43 2.3.3. Genome ...... 44 2.3.4. Virus entry ...... 44 2.3.5. Transcription and protein synthesis ...... 45 2.3.6. RNA packaging and virion assembly ...... 46 2.3.7. Innate immune evasion ...... 48 2.4. ...... 49 2.4.1. Virion structure ...... 51 2.4.2. Genome ...... 51 2.4.3. Replication cycle ...... 51 2.4.4. Virus entry ...... 52 2.4.5. Transcription, (+)ssRNA selection and packaging, replication ...... 52 2.4.6. Innate immune evasion ...... 54 2.5. Concluding remarks and future challenges to understand dsRNA virus biology ...... 55 2.6. References ...... 56 Contents vii

Chapter 3. Negative-strand RNA Viruses ...... 69

Rachel FEARNS 3.1. Introduction ...... 69 3.2. Replication cycles of negative-strand RNA viruses ...... 70 3.2.1. The order Mononegavirales ...... 70 3.2.2. The order ...... 73 3.2.3. The order Articulavirales ...... 77 3.2.4. The genus Deltavirus ...... 78 3.2.5. Summary of viral replication cycles ...... 80 3.3. The transcription and replication machinery of the negative-strand RNA viruses ...... 80 3.3.1. Overview of the different negative-strand RNA virus polymerases ...... 80 3.3.2. Orthomyxovirus polymerases and their transcription and replication mechanisms ...... 81 3.3.3. The bunyavirus polymerase ...... 85 3.3.4. The mononegavirus polymerases and their transcription and replication mechanisms ...... 86 3.3.5. Concluding remarks ...... 90 3.4. References ...... 91

Chapter 4. Viral Epitranscriptomics ...... 105

Rachel NETZBAND and Cara T. PAGER 4.1. Introduction ...... 105 4.1.1. What are epitranscriptomic marks? ...... 105 4.1.2. How are epitranscriptomic marks installed? ...... 106 4.2. The tools of RNA modification discovery ...... 106 4.2.1. Chromatography and mass spectrometry ...... 107 4.2.2. Sequencing methods for PTM detection ...... 109 4.3. RNA modifications deposited by viral enzymes ...... 113 4.3.1. Capping of 5’ end of viral RNA by viral methyltransferases .... 113 4.3.2. 2’O-methylation of viral RNA ...... 114 4.4. Editing of viral RNA by cellular enzymes ...... 120 4.4.1. Editing of uridine-to-pseudouridine (Ψ) ...... 121 4.4.2. Editing of adenosine-to-inosine ...... 123 4.5. Deposition of RNA modifications on viral RNA by cellular enzymes ...... 129

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4.5.1. Role of N6-methyladenosine (m6A) on viral gene expression .... 129 4.5.2. Role of 5-methylcytosine (m5C) in viral gene expression ...... 136 4.5.3. The viral epitranscriptome ...... 139 4.6. Conclusion ...... 140 4.7. References ...... 141

Chapter 5. Defective Viral Particles ...... 159

Carolina B. LÓPEZ 5.1. Introduction ...... 159 5.2. Discovery of defective viral genomes and early research ...... 160 5.3. Classes of defective viral genomes ...... 166 5.3.1. Mutations and frame shifts ...... 168 5.3.2. Deletion DVGs ...... 168 5.3.3. Copy-back and snap-back DVGs ...... 169 5.3.4. Others ...... 169 5.4. Impacts on the virus–host interaction ...... 170 5.4.1. Interference with virus replication ...... 170 5.4.2. Stimulation of the immune response ...... 171 5.4.3. Antivirals and vaccines ...... 173 5.4.4. Establishment of virus persistence ...... 174 5.4.5. Impact on virus spread ...... 175 5.5. Host factors affecting DVG accumulation and activity ...... 175 5.6. Conclusion ...... 176 5.7. References ...... 176

Chapter 6. Enteric Viruses and the Intestinal Microbiota ...... 197

Matthew PHILLIPS, Bria F. DUNLAP, Megan T. BALDRIDGE and Stephanie M. KARST 6.1. Introduction ...... 197 6.2. Enteric ...... 198 6.2.1. Intestinal microbiota enhance poliovirus stability ...... 200 6.2.2. Bacterial glycans facilitate virion attachment to target cells ..... 200 6.2.3. Intestinal microbiota promote poliovirus recombination ...... 200 6.3. Mouse mammary tumor virus ...... 201 6.3.1. MMTV binds LPS, which in turn promotes a tolerogenic immune environment conducive to viral persistence ...... 202 6.3.2. MMTV incorporates host LPS-binding proteins into its envelope ...... 202

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6.4. Reoviruses ...... 204 6.4.1. Intestinal microbiota enhance reovirus stability ...... 204 6.4.2. Immunostimulatory properties of bacterial flagellin inhibit infection ...... 206 6.4.3. Segmented filamentous bacteria have direct and indirect antiviral activity against rotavirus ...... 207 6.4.4. How to reconcile the seemingly contradictory observations of bacterial enhancement and bacterial suppression of rotavirus infection ...... 207 6.5. ...... 208 6.5.1. Intestinal microbiota can promote infection ...... 209 6.5.2. Intestinal microbiota can trigger antiviral immune responses during norovirus infection ...... 211 6.6. ...... 213 6.6.1. Host interferon responses reduce replication and infection ...... 214 6.6.2. Dysbiosis can occur after AstV infection ...... 214 6.6.3. In vivo and in vitro culture systems for AstV pathogenesis studies ...... 215 6.7. Overall conclusion ...... 216 6.8. References ...... 217

Chapter 7. Plant–Virus–Vector Interactions ...... 227

Swapna Priya RAJARAPU, Diane E. ULLMAN, Marilyne UZEST, Dorith ROTENBERG, Norma A. ORDAZ and Anna E. WHITFIELD 7.1. Introduction ...... 227 7.2. Non-circulative virus transmission ...... 228 7.2.1. Vectors of non-circulative viruses ...... 230 7.2.2. Virus–vector interactions are highly specific ...... 231 7.2.3. Capsid strategy ...... 232 7.2.4. Helper strategy ...... 232 7.3. Circulative virus transmission ...... 234 7.3.1. Vectors of circulative viruses ...... 234 7.4. Receptors in vectors of non-circulative viruses ...... 235 7.4.1. Receptors in aphid stylets ...... 236 7.4.2. Receptors in vector foreguts ...... 237 7.5. Receptors in vectors of circulative viruses ...... 237 7.5.1. Circulative virus binding and transcytosis ...... 237 7.5.2. Circulative virus receptors ...... 238 7.6. Circulative, propagative virus binding and entry ...... 239 7.6.1. Circulative, propagative viruses binding and entry ...... 239 x Virology

7.6.2. Receptors in vectors of circulative, propagative viruses ...... 241 7.6.3. Vertical transmission of propagative, circulative viruses ...... 242 7.7. Virus transmission morphs for non-circulative viruses ...... 243 7.8. “Omics” tools for studying virus–arthropod interactions ...... 243 7.9. Vector innate immunity in response to viruses ...... 247 7.10. Host and vector manipulation by plant viruses ...... 250 7.10.1. Indirect (plant-mediated) manipulation of insect vectors by plant viruses ...... 250 7.10.2. Direct manipulation of insect vectors by plant viruses ...... 260 7.10.3. Mode of transmission and virus manipulation of plant hosts leading to enhanced vector transmission ...... 262 7.11. Summary points ...... 263 7.12. Acknowledgments ...... 264 7.13. References ...... 265

Chapter 8. Evolution and Origin of Human Viruses ...... 289

Rachele CAGLIANI, Alessandra MOZZI, Chiara PONTREMOLI, Manuela SIRONI 8.1. Introduction ...... 289 8.2. Origin and ancient evolutionary history of human viruses ...... 290 8.2.1. Origin and ancient evolutionary history of human-infecting RNA viruses ...... 290 8.2.2. Origin and ancient evolutionary history of human-infecting reverse-transcribing viruses ...... 295 8.2.3. Origin and ancient evolutionary history of human-infecting DNA viruses ...... 298 8.3. Sources of viral genetic diversity ...... 303 8.4. Viral evolution and host range ...... 307 8.5. Recent evolution of human RNA viruses – selected examples ...... 313 8.6. Conclusion ...... 319 8.7. References ...... 320

List of Authors ...... 341

Index ...... 345