Advances in Virus Research (eBook)

Front Cover 1
Advances in Virus Research 4
Copyright Page 5
Contents 6
Chapter 1: Regulation of HIV-1 Alternative RNA Splicing and Its Role in Virus Replication 8
I. Introduction 9
II. HIV-1 Splicing Regulatory Elements 10
A. Cis-regulatory elements that activate and repress metazoan mRNA splicing 10
1. Core splicing signals and exon definition 10
2. Exonic and intronic splicing enhancers and silencers 11
3. Role of secondary structure 12
B. General strategy of HIV-1 RNA splicing 12
C. Intrinsic efficiency of HIV-1 splice sites 13
D. HIV-1 splice sites and their regulatory elements 15
1. Vif mRNA splice site: 3& prime
2. Vpr mRNA 3& prime
3. Tat mRNA 3& prime
4. Rev and env/nef 3& prime
5. Nef and tat, rev exon 2 splice site: 3& prime
6. HXB2 tev splice sites: 3& prime
7. Gag–pol splice sites: 3& prime
E. Alternative roles of the major splice donor sites 5ss D1 and D4 in HIV-1 replication 22
F. Effects of inclusion of small exons 2 and 3 on HIV-1 mRNA expression and stability 24
G. Effects of RNA secondary structure on HIV-1 splicing 24
H. Possible roles of HIV-1 Rev, Tat, and Vpr proteins in regulation of viral RNA splicing 25
III. Evidence for the Functional Importance of HIV-1 Splicing Regulatory Elements in Virus Replication 28
A. Sequence comparison of HIV-1 splice sites and regulatory elements 28
B. Mutations of HIV-1 regulatory elements inhibit virus replication 30
C. Overexpression and siRNA inhibition of cellular splicing factors affect HIV-1 splicing and inhibit virus replication 35
D. Changes in expression of cellular splicing factors during HIV-1 infection 36
IV. Strategies to Target HIV-1 Splicing with Antiviral Drugs 37
V. Conclusions and Perspectives 39
Acknowledgments 40
References 40
Chapter 2: New Insights into Flavivirus Nonstructural Protein 5 48
I. Introduction 49
II. The Methyltransferase Domain 51
A. 5& prime
B. MTase enzymatic activities 52
C. MTase structure 59
1. The core MTase subdomain 61
2. N-terminal GTP-binding subdomain 62
3. RNA-binding groove 63
D. MTase structure-function studies 64
1. GTP-binding studies 64
2. MTase activities 65
E. A model for flavivirus cap methylation 67
III. The RNA-Dependent RNA Polymerase Domain 68
A. Flavivirus RNA synthesis 68
B. RdRp activity of NS5 69
1. NS5 has RdRp activity 69
2. The flavivirus RdRp can initiate RNA synthesis de novo 70
3. Requirements for de novo initiation 71
4. Template requirements for RNA synthesis 72
C. RdRp structure 74
1. Overall NS5 RdRp structure 74
2. The palm subdomain 75
3. The fingers subdomain 77
4. The thumb subdomain 79
5. Initiation of RNA synthesis 80
6. Structure of the full-length NS5 81
D. Structure-function analysis 81
IV. NS5 Interactions 82
A. NS5 intramolecular interactions 82
B. The interaction of NS5 with viral RNA 83
C. The interaction of NS3 and NS5 84
D. The interaction of NS5 with host proteins 85
V. NS5 Phosphorylation 86
VI. NS5 Localization 88
A. Cellular localization of NS5 88
B. NS5 nuclear localization 89
VII. Emerging Roles for NS5 in Viral Pathogenesis 92
VIII. Conclusions and Future Perspectives 96
Acknowledgments 99
References 99
Chapter 3: Replication of the Hepatitis Delta Virus RNA Genome 110
I. Background 111
II. Polymerase(s) 113
III. Promoters and Priming 115
IV. Pausing and Switching 117
V. Replication in the Nucleus 119
VI. Role(s) of the Delta Antigen 120
VII. Host Factors 122
VIII. Viroid Analogy 123
IX. Conclusions and Outlook 123
Acknowledgments 124
References 124
Chapter 4: Recent Epidemiology of Tick-Borne Encephalitis: An Effect of Climate Change? 130
I. Introduction 131
II. Major Debatable Issues 134
III. The Ranges of Main Tick Vectors: Are They Really Expanding? 135
IV. Tick Abundance and TBE Virus Prevalence: Have They Changed? 136
V. Tick Expansion to the Cities: Is It Related to Climate Change? 138
VI. What Is Known About Newly Formed TBE foci? 140
VII. Anthropurgic TBE foci: What Are the Principles of Their Formation? 141
VIII. Since When Has TBE Morbidity Increased in the Cities? 142
IX. What Are the Main Causes of Changes in Parameters of TBE Morbidity? 143
X. Conclusions 144
Acknowledgment 145
References 145
Index 152
Color Plates 158