Advances in Virus Research

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Front Cover ; Advances in Virus Research ; Copyright Page ; Contents ; Chapter 1: Regulation of HIV-1 Alternative RNA Splicing and Its Role in Virus Replication ; I. Introduction; II. HIV-1 Splicing Regulatory Elements; A. Cis-regulatory elements that activate and repress metazoan mRNA splicing ; 1. Core splicing signals and exon definition ; 2. Exonic and intronic splicing enhancers and silencers ; 3. Role of secondary structure ; B. General strategy of HIV-1 RNA splicing; C. Intrinsic efficiency of HIV-1 splice sites; D. HIV-1 splice sites and their regulatory elements. 1. Vif mRNA splice site: 3 ss A1 2. Vpr mRNA 3 -splice site: 3 ss A2 ; 3. Tat mRNA 3 -splice site: 3 ss A3 ; 4. Rev and env/nef 3 -splice sites: 3 ss A4c, A4a, A4b, and A5 ; 5. Nef and tat, rev exon 2 splice site: 3 ss A7 ; 6. HXB2 tev splice sites: 3 ss A6 and 5 ss D6 ; 7. Gag-pol splice sites: 3 ss A1A and 5 ss D1A ; E. Alternative roles of the major splice donor sites 5ss D1 and D4 in HIV-1 replication; F. Effects of inclusion of small exons 2 and 3 on HIV-1 mRNA expression and stability; G. Effects of RNA secondary structure on HIV-1 splicing. H. Possible roles of HIV-1 Rev, Tat, and Vpr proteins in regulation of viral RNA splicingIII. Evidence for the Functional Importance of HIV-1 Splicing Regulatory Elements in Virus Replication; A. Sequence comparison of HIV-1 splice sites and regulatory elements; B. Mutations of HIV-1 regulatory elements inhibit virus replication; C. Overexpression and siRNA inhibition of cellular splicing factors affect HIV-1 splicing and inhibit virus replication; D. Changes in expression of cellular splicing factors during HIV-1 infection; IV. Strategies to Target HIV-1 Splicing with Antiviral Drugs. V. Conclusions and PerspectivesAcknowledgments; References; Chapter 2: New Insights into Flavivirus Nonstructural Protein 5 ; I. Introduction; II. The Methyltransferase Domain; A. 5 -RNA cap formation ; B. MTase enzymatic activities; C. MTase structure; 1. The core MTase subdomain ; 2. N-terminal GTP-binding subdomain ; 3. RNA-binding groove ; D. MTase structure-function studies; 1. GTP-binding studies ; 2. MTase activities ; E.A model for flavivirus cap methylation; III. The RNA-Dependent RNA Polymerase Domain; A. Flavivirus RNA synthesis; B. RdRp activity of NS5; 1. NS5 has RdRp activity. 2. The flavivirus RdRp can initiate RNA synthesis de novo 3. Requirements for de novo initiation ; 4. Template requirements for RNA synthesis ; C. RdRp structure; 1. Overall NS5 RdRp structure ; 2. The palm subdomain ; 3. The fingers subdomain ; 4. The thumb subdomain ; 5. Initiation of RNA synthesis ; 6. Structure of the full-length NS5 ; D. Structure-function analysis; IV. NS5 Interactions; A. NS5 intramolecular interactions; B. The interaction of NS5 with viral RNA; C. The interaction of NS3 and NS5; D. The interaction of NS5 with host proteins; V. NS5 Phosphorylation; VI. NS5 Localization