Understanding Retroviruses and HIV Study Guide
This guide provides a comprehensive overview of retroviruses, their unique replication strategies involving reverse transcriptase, their integration into host genomes, and the specific life cycle of HIV. It covers key concepts such as the Central Dogma, provirus formation, and the viral oncogene hypothesis, making it suitable for students and researchers in virology and related fields.
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Viral Life Cycle, Assembly, and Egress
The Viral Life Cycle and Entry
The viral life cycle involves viral attachment, entry, transcription of viral mRNAs, synthesis of viral proteins and new viral genomes, assembly, and release and maturation of viral particles.
- Viral life cycle
- Viral attachment
- Viral entry
- Transcription of viral mRNAs
- Synthesis of viral proteins
- Synthesis of viral genomes
- Assembly of virus
- Release and maturation of viral particle
- Penetration of host cell membranes
- Uncoating and disassembly
- Cytosol targeting
- Nucleus targeting
- Anti-viral therapy targets
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Viral Attachment and Cell Entry Mechanisms
Viruses utilize adhesion and entry receptors to bind to host cell surface molecules such as proteins, carbohydrates, and lipids.
- Viral receptors
- Adhesion receptors
- Entry receptors
- Host range
- Tissue tropism
- Epithelial cells
- Apical and basal surfaces
- Transcytosis
- Cell surface molecules
- Lipid rafts
Viral Attachment and Receptor Identification
Early investigations of viral receptors used enzymes to characterize cell surface components and technologies like monoclonal antibodies to identify how virions attach to receptors.
- Proteases
- Glycosidases
- Lipases
- Neuraminidase
- Sialic acid
- Monoclonal antibodies
- Susceptible cell
- Permissive cell
- Protruding fibers
- Loops
- Canyon
- Viral envelope glycoproteins
- Co-receptor
- HIV CD4
- Hepatitis C virus
Viral Attachment and Entry Mechanisms
Viruses use capsids and envelopes to protect genomes during attachment, penetration, and uncoating processes via pH-independent or pH-dependent pathways.
- Viral attachment
- Genome penetration
- Uncoating and disassembly
- Enveloped vs. non-enveloped viruses
- Membrane fusion
- Endocytosis
- pH-independent pathway
- pH-dependent pathway
- Receptor-mediated endocytosis
- Endosomal membrane disruption
- Pore formation
- Lysosomal uncoating
- Nuclear transport
- Nuclear localization sequence
Virus Assembly and Progeny Egress
Processes involving the assembly of structural units, incorporation of nucleic acid genomes, and the release of newly assembled viral progeny through budding or lysis.
- Structural unit formation
- Coat assembly
- Chaperone-assisted assembly
- Packaging signals
- Budding
- Lysis
- Maturation
- Self-assembly
- Polyprotein precursors
- Viral scaffolding proteins
- Procapsids
- Autoproteolytic cleavage
Viral Genome Packaging and Assembly
Viral genomes are packaged inside nascent viral particles through concerted or sequential assembly modes involving cis-acting signals and trans-acting viral factors.
- Concerted assembly
- Sequential assembly
- Cis-acting signals
- Trans-acting viral factors
- Influenza A virus assembly
- HIV-1 Y site
- Nucleocapsid protein
- Segmented genome packaging
- Random packaging
- Selective packaging
- vRNP segments
Viral Assembly, Egress, and Maturation
Mechanisms of virion maturation via proteolytic processing.
- Release of viral particles
- Non-enveloped viruses lysis
- Enveloped viruses budding
- Exocytosis
- Actin tails
- Poxviruses
- Viroporins
- ESCRT machinery
- Virion maturation
- Proteolytic processing
- Protein cleavage
- Retroviruses
- Gag precursor cleavage
Intracellular Transport and Virus Assembly
Viral components must be actively transported to assembly sites through cellular compartments and the secretory pathway using motor proteins and vesicular transport.
- Intracellular trafficking
- Virus assembly
- Eukaryotic cell compartmentalization
- Secretory pathway
- Vesicular transport
- Motor proteins
- Cytoskeletal tracks
- Actin fibers
- Microtubules
- Snare proteins
- Rab proteins
- Membrane fusion
Translocation and Transport of Viral Proteins
Viral membrane proteins undergo translocation into the ER lumen, modification within the ER and Golgi apparatus, and transport through the secretory pathway.
- Translocation of viral membrane proteins
- Signal Recognition Protein (SRP)
- Hydrophobic stop signals
- Glycosylation
- Disulfide bond formation
- Protein folding by molecular chaperones
- Oligomerization
- Proteolytic cleavage
- Viral genome transport
- Viral inhibition of intracellular transport
- MHC class I inhibition
- Redirection of transport systems
Retrovirus Structure, Genome, and Replication Mechanisms
Introduction to Retroviruses and HIV
Retroviruses are enveloped, single stranded (+) RNA viruses that replicate through a DNA intermediate using reverse transcriptase.
- Retroviridae Family
- Reverse transcriptase
- Provirus state
- Viral Oncogene Hypothesis
- Central Dogma of Molecular Biology
- Retrovirus Classification
- Simple and Complex retroviruses
- Oncogenic viruses
- HIV life cycle
- Reverse transcription and integration
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Retrovirus Genome Organization and Reverse Transcription
Retrovirus particles contain two copies of genomic RNA that utilize tRNA primers for the initiation of reverse transcription by reverse transcriptase.
- Retrovirus genome organization
- Pseudodiploid
- tRNA primer
- Primer Binding Site (PBS)
- Reverse transcription
- RNA-dependent DNA polymerase
- Complementary DNA (cDNA)
- Reverse transcriptase catalytic activities
- DNA-directed DNA polymerase
- Helicase
- RNaseH
- Low fidelity
Retroviral Replication and Integration Mechanisms
Retroviruses undergo reverse transcription of the viral RNA genome into cDNA, which is integrated into the host genome by integrase to form proviral DNA.
- Reverse transcription
- HIV polypurine tract
- Long terminal repeat (LTR)
- Recombination during reverse transcription
- Copy choice
- Strand assimilation
- Integration
- Integrase
- Proviral DNA
- Host RNA polymerase II
- Retroviral life cycle
Mechanisms of Viral Replication and Translation
RNA Virus Replication Mechanisms
RNA-dependent RNA Polymerases catalyze template-directed RNA synthesis and utilize viral accessory proteins and cellular proteins to facilitate replication.
- RNA-dependent RNA Polymerases (RdRPs)
- Template-directed RNA synthesis
- RNA secondary structures
- Viral accessory proteins
- Helicases
- Host protein hijacking
- Subcellular localization of replication components
RNA Replication and mRNA Synthesis Mechanisms
RNA-dependent RNA polymerase initiation mechanisms include de-novo initiation, cap snatching, and protein priming, alongside processes for polyA tract synthesis and mRNA circularization.
- RdRp initiation mechanisms
- De-novo initiation
- Protein priming
- VPg polyuridylation
- Reiterative copying stuttering
- mRNA circularization
- Ribosome
Mechanisms of Viral RNA Replication Switching
RNA viruses utilize different switching mechanisms to transition from mRNA production to genome RNA synthesis.
- mRNA production
- genome RNA synthesis
- nonstructural proteins
- subgenomic promoter
- subgenomic RNA
- different polymerases for different functions
- antiterminator activity
- intergenic regions
- N protein
- dsRNA viruses
- reovirus cores
Mechanisms of Viral DNA Replication
Viral DNA replication involves genome composition, transcription of viral mRNAs by cellular RNA polymerases, and DNA synthesis through processes like semi-discontinuous replication.
- Genome composition
- Viral mRNA transcription
- Cellular RNA polymerases
- Nuclear localization
- Cis-acting sequences
- Trans-acting factors
- Transcriptional control region
- Viral gene expression regulation
- DNA synthesis principles
- Semi-discontinuous DNA synthesis
- Leading strand synthesis
- Okazaki fragments
- DNA replication machinery
RNA Virus Replication and Genome Composition
RNA virus replication strategies and genome composition include (+) ssRNA, (-) ssRNA, ambisense, and dsRNA viruses.
- Genome composition
- Plus sense single stranded RNA viruses
- Negative or ambisense RNA viruses
- Viral RNA synthesis
- RNA genome polarity
- Translation-competent mRNAs
- RNA-dependent RNA polymerase (RdRp)
- Antigenomic RNA
- Subgenomic promoter
- Ribonucleoprotein complex
- dsRNA replication
Viral pre-mRNA Processing and Translational Control
Viral mRNAs undergo RNA processing including 5’ capping, 3’ polyadenylation, and splicing to conform to host cell translation requirements and regulate gene expression.
- 5’ capping
- 3’ polyadenylation
- RNA splicing
- Alternative splicing
- IRES elements
- Nuclear export
- Temporal control of gene expression
- Inhibition of cellular mRNA translation
- mRNA stability
Eukaryotic and Viral Translation Strategies
Eukaryotic protein synthesis involves initiation, elongation, and termination, while viruses utilize diverse strategies like leaky scanning, IRES elements, polyprotein synthesis, and ribosomal frameshifting.
- Eukaryotic protein synthesis
- Translation initiation
- eIF factors
- Elongation
- eEF factors
- Termination
- eRF factors
- Leaky scanning
- Methionine-independent initiation
- Ribosome shunting
- Internal Ribosome Entry Site (IRES)
- Polyprotein synthesis
- Ribosomal frameshifting
- Termination of suppression
- Translation reinitiation
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