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Copyrighted Material Contents Introduction ....................................... xi María-Carla SALEH and Félix AUGUSTO REY Chapter 1. DNA Viruses ............................... 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 virus, 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 vi Virology 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. Rotaviruses .................................... 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. Orbiviruses .................................... 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 Bunyavirales .......................... 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 viii Virology 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 picornaviruses ............................. 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 Contents ix 6.4. Reoviruses .................................... 204 6.4.1. Intestinal microbiota enhance reovirus stability ............ 204 6.4.2. Immunostimulatory properties of bacterial flagellin inhibit rotavirus 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. Noroviruses .................................... 208 6.5.1. Intestinal microbiota can promote norovirus infection ........ 209 6.5.2. Intestinal microbiota can trigger antiviral immune responses during norovirus infection ...................... 211 6.6. Astroviruses ................................... 213 6.6.1. Host interferon responses reduce astrovirus 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
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