Chapter
1 - Retrovirus Receptor Interactions and Entry
ENVELOPE GLYCOPROTEINS: DOMAIN STRUCTURE
RETROVIRUS ENTRY RECEPTORS
THE BASICS OF MEMBRANE FUSION
DO RECEPTOR INTERACTIONS CONTRIBUTE TO THE ENVELOPE PROTEINS FUNCTIONS THAT DRIVE ENTRY?
Conserved Motifs in Envelope Proteins Are Critical to Regulation of Fusion
Regulation by Control of the Conformation of Surface Subunit
Regulation by Control of Disulfide Bond Isomerization and Surface Subunit Conformation
Lentiviruses: Receptor-Triggered Conformational Changes in the Surface Subunit
Gammaretroviruses: Receptor- and Cellular Protease–Driven Disulfide Bond Isomerization
Alpharetroviruses: Receptor- and Low pH-Driven Disulfide Bond Isomerization
DO ENV–RECEPTOR INTERACTIONS CONTRIBUTE TO PATHOGENESIS?
CD4+ T-Cell Depletion and AIDS
Neurological Damage and HAM/TSP
Mutations That Adapt Virus to Low Receptor Levels Can Also Increase Pathogenicity
Envelope Protein–Driven Neoplasia in Betaretrovirus Infection
HOST DEFENSES THAT INHIBIT RETROVIRAL ENTRY ALSO DRIVE ENVELOPE PROTEIN VARIATION
Challenges in Vaccine Development
Interferon-Induced Transmembrane Proteins and Envelope Proteins Variation
COEVOLUTION OF VIRUS AND RECEPTOR
CAPTURED RETROVIRAL ENVELOPE PROTEINS IN THE DEVELOPMENT OF MAMMALIAN PLACENTA AND MALE MUSCLE MASS
2 - Cellular Factors That Regulate Retrovirus Uncoating and Reverse Transcription
A BRIEF DESCRIPTION OF EARLY EVENTS OF INFECTION
MONITORING THE COURSE OF INFECTION IN EARLY STAGES
Monitoring Viral Nucleic Acids
Monitoring Incoming Viral Proteins
HOST FACTORS PROMOTING EARLY EVENTS OF INFECTION
Breaking and Entering: Subcortical Actin
Factors Affecting Reverse Transcription
Cytoskeleton and Motors: Trafficking
Cyclophilin A, a Host Factor Binding Capsid
Modifications of Viral Proteins During Infection
HOST FACTORS RESTRICTING INFECTION IN EARLY STAGES OF INFECTION
Fv1, a Gene for Resistance to the Friend Leukemia Virus
TRIM5α, a Major Postentry Block
TRIM-Cyp: Evolution of a Restriction Factor by Gene Fusion
Lv2: An Entry-Specific Block
APOBECs, the Cytidine Deaminases
MX2, Another Factor Targeting Capsid
More Restriction Factors?
SENSING AND RESPONDING TO INFECTION: INNATE IMMUNITY
RIG-I and MDA5 as Retroviral Sensors
cGAS Involvement in Sensing Infection
CONCLUSIONS: PARTING WORDS
3 - Nucleoporins in Retroviral Replication: What’s Nup Got to Do with It?
NUCLEAR PORE COMPLEXES, NUCLEOPORINS, AND NUCLEOCYTOPLASMIC TRANSPORT
NUCLEOPORINS IMPLICATED IN RETROVIRAL REPLICATION
Normal Cellular Functions of the Nup358/RanBP2 Nuclear Pore Complex Protein
Functions of Nu358/RanBP2 in Retroviral Replication
Normal Cellular Functions of the Nup214/CAN Nuclear Pore Complex Protein
Functions of Nup214/CAN in Retroviral Replication
Normal Cellular Functions of the Nup98 Nuclear Pore Complex Protein
Functions of Nup98 in Retroviral Replication
Normal Cellular Functions of the Nup85 and Nup160 Components of the Nup107–160 Nuclear Pore Complex
Functions of the Nup107–160 Complex (Y-Complex) during Retroviral Replication
Normal Cellular Functions of the Nup62 Nuclear Pore Complex Protein
Functions of Nup62 in Retroviral Replication
Normal Cellular Functions of the Nup155 Nuclear Pore Complex Protein
Functions of Nup155 in Retroviral Replication
Normal Cellular Functions of the Nup153 Nuclear Pore Complex Protein
Functions of Nup153 in Retroviral Replication
Normal Cellular Functions of the Tetratricopeptide Repeat Nuclear Pore Complex Protein
Functions of Tetratricopeptide Repeat in Retroviral Replication
CAUTION: DEPLETION OF ANY SINGLE MULTIFUNCTIONAL NUP CAN MODIFY OVERALL NPC ARCHITECTURE
THE IMPORTANCE OF FG-REPEAT NUPS TO DISEASE
VIRUSES COMMONLY CAUSE THE DISPLACEMENT OF FG–NUPS TO REMODEL NPCS
4 - Virus–Host Interactions in Retrovirus Integration
INTEGRASE-INTERACTING PROTEINS
LENS EPITHELIUM–DERIVED GROWTH FACTOR/P75
HEPATOMA-DERIVED GROWTH FACTOR LIKE 2 (HDGFL2)
BROMODOMAIN AND EXTRA-TERMINAL DOMAIN PROTEINS
B′-PROTEIN PHOSPHATASE 2A (PP2A)
HIV-1 CA–INTERACTING PROTEINS
ALLOSTERIC IN INHIBITORS THAT TARGET THE LEDGF/P75–IN INTERACTION
5 - Transcriptional Control and Latency of Retroviruses
RETROVIRAL INTEGRATION OCCURS AT TRANSCRIPTIONALLY ACTIVE SITES IN HOST GENOME
TRANSCRIPTIONAL REGULATION BY ENDOGENOUS RETROVIRUSES
Retroviral Elements Are Prominent in All Jawed Vertebrate Genomes
Endogenous Retroviruses Can Function as Long-Range Transcriptional Enhancers
Endogenous Retroviruses Regulate the Potency of Stem Cells
RETROVIRAL GENOME COMPLEXITY CONFERS A BENEFIT FOR TRANSCRIPTIONAL REGULATION
Transcriptional Regulation in Simple Retroviruses
Retroviral Capture of Cellular Genes for Transcription Factors or Signaling Kinases
Retroviral Use of Hormone Response Elements in Long Terminal Repeat Enhancer
Transcriptional Silencing of Simple Retroviruses
Complex Retroviruses Encode Transactivator Proteins
TRANSCRIPTIONAL CONTROL OF HIV-1
Clinical Importance of HIV-1 Proviral Transcription
HIV-1 5′ Long Terminal Repeat Contains the Viral Promoter and Enhancer
RNA Polymerase II Transcriptional Initiation of the HIV-1 Provirus
HIV-1 Tat Activates RNA Polymerase II Elongation
CDK11 and HIV-1 3′ End Processing
Establishment of Latent Infection
Maintenance of Latent Infection
Reactivation of Latent Virus
FUTURE RESEARCH OF RETROVIRAL TRANSCRIPTION
HIV-1 Latency and the Need for a Functional Cure
Endogenous Retroviruses in Stem Cells and Cancer
6 - Teetering on the Edge: The Critical Role of RNA Processing Control During HIV-1 Replication
ROLE OF HNRNPS IN THE REGULATION OF HIV-1 RNA PROCESSING
ROLE OF SR PROTEINS IN THE REGULATION OF HIV-1 RNA PROCESSING
MANIPULATION OF HIV-1 RNA PROCESSING WITH SMALL MOLECULES
7 - Cellular RNA Helicases Support Early and Late Events in Retroviral Replication
RNA HELICASE AND RETROVIRUSES IN THE ADVENT OF “OMICS TECHNOLOGY”
EARLY EVENTS: REVERSE TRANSCRIPTION AND INTEGRATION
DHX9/RNA HELICASE A ACTIVITY IN THE GENOMIC RNP
MOV10 ACTIVITY IN VIRIONS REMAINS UNDEFINED
LATE EVENTS: PROVIRUS TRANSCRIPTION, PRIMARY RNA PROCESSING, EXPORT, TRANSLATION, FORMATION OF GENOMIC RNP
DHX9, Bridging RNA Polymerase to Transcription Coactivators
Shuttling RNA Helicase in Nucleocytoplasmic Transport of Retroviral RNA
NUCLEAR CAP–BINDING PROTEINS AND RNA HELICASE: TRANSLATION EVADING NONSENSE RNA–MEDIATED DECAY
STEADY-STATE TRANSLATION: SWITCHING 5′CAP–BINDING PROTEINS TO GAIN EIF4E
THERAPEUTIC TARGETING AT THE INTERFACE OF RNA HELICASE AND COGNATE RETROVIRAL RNA
8 - Role of Host Factors in the Subcellular Trafficking of Gag Proteins and Genomic RNA Leading to Virion Assembly
NUCLEAR EXPORT OF VIRAL RNAS
Unspliced Viral RNA Export in Simple Retroviruses
The Constitutive Transport Element of MMTV
Export of Unspliced RNA in Rous Sarcoma Virus
Spumaretrovirus RNA Nuclear Export
RETROVIRAL GENOME TRAFFICKING IN THE CYTOPLASM
Relationship Between Viral RNA Export and Virus Assembly
Transport of Unspliced Viral RNA Through the Cytoplasm to the Assembly Site
Dimerization of Retroviral Genomic RNA
RETROVIRAL GAG PROTEIN TRAFFICKING
Nuclear Trafficking of Retroviral Gag Proteins
Foamy Virus Gag Association With Chromatin
Transport of Gag Proteins in the Cytoplasm
Role of Cytoskeletal Proteins and Microtubule-Organizing Center in Gag Transport
Multivesicular Bodies and Endosomal Proteins in Gag Trafficking
Role of Myristoylation and Lipid Binding in Gag Membrane Targeting
Multivesicular Body and Endosomal Sorting Complexes Required for Transport Pathway Interactions With Gag Late Domains
Nedd4 and E3 Ubiquitin Ligases
Tsg101 as a Central Player in Wide Range of Gag Late Domain Interactions
Alix/AIP-1 Interactions With HIV Gag Proteins
Late Domains in EIAV, MLV, and Foamy Virus Gag Proteins
Endophilin 2 in Murine Leukemia Virus Gag Trafficking
Association of Gag With tRNA Synthetases
FACTORS THAT INTERACT WITH GAG OR VIRAL RNA TO RESTRICT VIRUS REPLICATION
Host Restriction Factors That Interfere With Gag Functions Early or Late in Replication
9 - Tumor Suppressor Gene 101: A Virus’ Multifunctional Conduit to the ESCRT Trafficking Machinery
The Endosomal Sorting Complex Required for Transport Machinery
Endosomal Sorting Complexes Required for Transport Participation in Cellular Processes
Endosomal Sorting Complexes Required for Transport Participation in Virus Budding
TUMOR SUPPRESSOR GENE 101 STRUCTURE
Tsg101-UEV PTAP-Binding Pocket
Tsg101-UEV Ub-Binding Pocket
Ub- and PTAP-Binding Pockets: Is There Cross Talk?
TUMOR SUPPRESSOR GENE 101 PARTICIPATION
Tumor Suppressor Gene 101 Participation in the Cellular Endocytic Pathway
Tumor Suppressor Gene 101 Participation in Virus Budding
CELLULAR FACTORS THAT WORK WITH TUMOR SUPPRESSOR GENE 101
Convergence of Tsg101-Ub-Nedd4-Alix Participation
TUMOR SUPPRESSOR GENE 101 ROLE IN BUDDING OF OTHER VIRUSES
10 - The Role of Lipids in Retroviral Replication
Composition of Cellular Membranes
Composition of Viral Membranes
LIPIDS IN RETROVIRAL ENTRY
Role of Cholesterol in Retroviral Entry
Role of Sphingolipids in Retroviral Entry
Role of Phospholipids in Retroviral Entry
Trafficking of Gag and Sites of Retroviral Assembly
Gag–Membrane Interactions
Lipids in Retroviral Assembly
Role of Cholesterol in Retroviral Assembly
Role of PI(4,5)P2 in Retroviral Assembly
Gag Binding to Giant Unilamellar Vesicles
LIPIDS IN RETROVIRAL CELL–CELL TRANSFER
Retroviral Accessory Proteins and Lipid Microdomains
INHIBITION OF RETROVIRAL REPLICATION WITH LIPID-MODIFYING AGENTS
Cholesterol Modifying Agents
Inhibitors of Sphingolipid Synthesis
11 - Cellular Immune Responses to Retroviruses
STEPS OF THE RETROVIRUS INFECTION PATHWAY TARGETED BY THE HOST INTRINSIC/INNATE RESPONSE
HOST PATHWAYS IMPLICATED IN CELLULAR CONTROL OF RETROVIRUS INFECTION
SUBVERSION OF CELLULAR IMMUNE RESPONSES BY RETROVIRUSES
12 - Noncoding RNAs in Retrovirus Replication
HOST RNAS PACKAGED INTO VIRIONS
High-Throughput RNA-Sequencing Studies
LONG NONCODING RNA AND ENDOGENOUS RETROVIRUSES
Large Intergenic RNA–p21: HIV-1
Antisense Protein RNA: HIV-1
Long Noncoding RNA 00173: HIV-1
FUNCTIONAL TRANSACTIVATING RESPONSE ELEMENT RNAS
RNA INTERFERENCE AND MIRNAS
RNAi, miRNA, and siRNA Production
Cellular MicroRNAs Made in Response to Viral Infections
Viral MicroRNAs Encoded Within Genomes
Viral Suppressors of RNA Silencing
13 - Cellular Control of Endogenous Retroviruses and Retroelements
Long Terminal Repeat Retrotransposons and Endogenous Retroviruses Fig. 13.1
Non-Long Terminal Repeat Retrotransposons
Long Interspersed Elements
Short Interspersed Elements
Chimeric Short Interspersed Elements
Frequencies of Retrotransposition
Retroelement Activities and Impacts
CONTROL OF RETROELEMENT EXPRESSION
Retroelement Transcription Patterns Favor Self-Preservation
Regulation of Retroelements in Somatic Cells by RNA Interference Fig. 13.2
Regulation of Retroelements in Germline and Embryonic Stem Cells
Sequence-Specific Suppression of Retroelements
Neuronal Activity of Retroelements
Roles for Retroelements in Cancer Initiation and Progression
REGULATION OF RETROELEMENTS BY THE INNATE IMMUNE SYSTEM
Regulation of Innate Immunity by Endogenous Retrovirus Sequences Fig. 13.3
Sensing of Retroelements by Innate Immunity
Direct Control of Retroelements by Innate Immunity
14 - Strategies to Discover Novel Cellular Factors Involved in Retrovirus Replication
IDENTIFYING PROTEIN–PROTEIN INTERACTIONS IN RETROVIRUSES USING TWO-HYBRID SCREENS
Using Gag Proteins as Bait
Additional Retroviral Proteins Used as Bait
MASS SPECTROMETRY APPROACHES TO DISCOVERY OF RETROVIRUS–CELL PROTEIN–PROTEIN INTERACTIONS
Mass Spectrometry to Identify Proteins Packaged Into Virus Particles
Mass Spectrometry to Identify Host Proteins Interacting With HIV-1 Proteins
Affinity Purification Approaches
Liquid Chromatography Coupled to Tandem Mass Spectrometry
Multidimensional Protein Identification Technology Mass Spectrometry
MASS SPECTROMETRY USING VIRAL DNA AS BAIT
HIV-1 5′ Untranslated Regions as Bait
MASS SPECTROMETRY USING VIRAL RNA AS BAIT
HIV-1 Subgenomic RNAs as Bait
Retroviral 5′Untranslated Regions as Bait
Full-Length HIV-1 RNA Used as Bait
RNA INTERFERENCE AND GENOME-WIDE SCREENS TO ASSESS THE CONTRIBUTION OF HOST FACTORS TO VIRUS REPLICATION
Small Interfering RNA Screens
Short Hairpin RNA Screens
Metaanalysis of siRNA Screens in HIV-1 Replication
Genome-Wide Analysis of Retrotransposition in Yeast
HOST GENOME EDITING USING CRISPR/CAS-9 TO FIND RETROVIRUS DEPENDENCY GENES
GAIN-OF-FUNCTION GENETIC APPROACHES USING CDNA OVEREXPRESSION SCREENS
IDENTIFICATION OF CELLULAR RNAS THAT INTERACT WITH RETROVIRUSES
Host RNAs Packaged Into Retrovirus Particles
RNA Sequencing Techniques