introduction to virology casey d. morrow, ph.d. department of cell biology [email protected]
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Introduction to Virology Casey D. Morrow, Ph.D. Department of Cell Biology [email protected]. Viral replication : How viruses exploit cells to make new viruses Viral pathogenesis : How virus replication causes disease and how viruses escape/interact with the immune system. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Introduction to Virology Casey D. Morrow, Ph.D. Department of Cell Biology caseym@uab.edu](https://reader035.vdocuments.mx/reader035/viewer/2022062302/56816450550346895dd61a25/html5/thumbnails/1.jpg)
Introduction to VirologyCasey D. Morrow, Ph.D.
Department of Cell [email protected]
• Viral replication: How viruses exploit cells to make new viruses
• Viral pathogenesis: How virus replication causes disease and how viruses escape/interact with the immune system
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http://www.bioteach.ubc.ca/MolecularBiology/AMonksFlourishingGarden/
The DNA -> RNA -> Protein Pathway
RNA Polymerase = enzyme that
makes mRNA from the DNA gene template
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Characteristics of Viruses• “Filterable agents” – Pass through filters that capture bacteria
• Obligate intracellular parasites
• Minimal genetic information, efficient
• Rely on host cell machinery to fulfill replication cycle
• Assembled from building blocks encoded by the virus (don’t divide like cells)
• Absolutely require host cell for replication to produce proteins required to synthesize new viral genomes and the building blocks of the virus structure
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For a Virus to be Successful:
• Capable of transmission through potentially harsh environmental conditions
• Traverse skin or other barriers of the host
• Must adapt to the biochemical machinery of the host cell for replication
• Escape elimination by the host immune response
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Basic Components of a Virion
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Virus Classification• Size• Morphology• Genome Type (DNA or RNA)• Means of Replication
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Relative Sizes of Viruses
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General Structure of Viruses
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Genome Contents of Viruses
• RNA• Single-strand• Double-strand• Linear• segmented
• DNA• Double-strand• Single-strand• Linear• Circular
http://gsbs.utmb.edu/microbook/images/fig41_6.JPG
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Naked vs. Enveloped Viruses• Naked Capsids
• Withstand harsh environmental conditions
• Resistant to drying, acids, detergents
• Many are transmitted fecal-oral route
• Enveloped Viruses• Can’t dry out• Not stable in acid• General must remain in body fluids (respiratory, blood)
http://www.cat.cc.md.us/courses/bio141/lecguide/unit2/viruses/images/u2fig2b.jpg
http://www.tarvacin.com/media/gif/EnvelopedVirusStructure.gif
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Icosahedral Capsid Assembly
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Examples of Icosahedral Capsids
1. Equine Herpesvirus Nucleocapsid
2. Simian Rotavirus
3. Reovirus type 1 virion
4. Intermediate partice: Reovirus
5. Inner core particle (Reovirus)
6. Human Papillomavirus type 19
7. Mouse Polyomavirus
8. Cauliflower Mosaic Virus
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General Enveloped Virus Structure
http://www.schoolscience.co.uk/content/5/biology/mrc/hiv/page2.html
HIVInfluenza
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Example Envelope Glycoprotein: Influenza Hemagglutinin
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Steps of Virus Replication Cycle
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Recognition of Cells and Attachment
Sialic acid: bound by Influenza virusHIV
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Steps of Virus Replication Cycle
Cell Entry:
Naked Viruses: Typically endocytosis
Enveloped Viruses: Typically cell fusion
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Synthesis of New Viral Components
• Viral Nucleic Acids• mRNA’s encoding viral proteins• New viral genomes for encapsidation into new virions (viral particles)
• Viral Proteins• Enzymes and other proteins required for viral transcription and genome replication
• Structural proteins (capsid proteins, viral glycoproteins)
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http://www.bioteach.ubc.ca/MolecularBiology/AMonksFlourishingGarden/
The DNA -> RNA -> Protein Pathway
RNA Polymerase = enzyme that
makes mRNA from the DNA gene template
![Page 20: Introduction to Virology Casey D. Morrow, Ph.D. Department of Cell Biology caseym@uab.edu](https://reader035.vdocuments.mx/reader035/viewer/2022062302/56816450550346895dd61a25/html5/thumbnails/20.jpg)
DNA Virus Transcription• Generally use the host cell’s DNA-dependent RNA Polymerase II to make mRNA’s
• Generally the DNA genomes go to the nucleus (some integrate into chromosomal DNA)
• One exception: Poxvirus family – Replicates only in the cytoplasm of cell so can’t use host cell’s RNA Polymerase II; instead, makes its own enzymes for transcription of mRNA’s
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RNA Virus Transcription• Many replicate entirely in the cytoplasm of the cell
• Must encode their own enzymes (RNA-dependent RNA polymerases) for transcription of mRNA and to replicate their full-length RNA genomes
• REASON: The host cell has no enzymes for generating new viral RNA genomes using an RNA template
• PLUS-STRAND RNA VIRUSES: Genomes same sense as mRNA
• MINUS-STRAND RNA VIRUSES: Genomes opposite sense as mRNA
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Replication of Viral Genomes• DNA Viruses:
• DNA-dependent DNA polymerases to make new DNA copies from DNA templates
• Some use cellular DNA polymerases• Others encode their own DNA polymerases
• RNA Viruses:• Use RNA-dependent RNA polymerases to make new RNA copies from RNA templates
• Encoded by the virus• Plus-strand versus minus-strand
• Retroviruses (example: HIV):• Genome in the viral particle is single-strand RNA• Packages Reverse Transcriptase• RNA DNA Integrated into chromosomal DNA• New viral RNA genomes transcribed in the nucleus by host cell polymerase
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Viral Protein Synthesis• All viruses depend on host cell translation machinery (ribosomes, tRNA, post-translational modifications) to generate viral proteins from mRNA templates
• Different strategies for compactness/efficiency:
• Separate mRNA’s for each viral protein
• Polyprotein strategy• Multiple proteins encoded on one mRNA• Individual proteins are derived from polyprotein by enzymatic cleavages catalyzed by proteases
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Polyprotein Strategy
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Assembly and Release
• Enveloped Viruses: typically exit by budding from the cell
• Naked viruses: typically exit through cell lysis
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Lytic Virus Growth Curve
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Viral Budding from Cell Membrane
http://www.itech.pjc.edu/fduncan/mcb1000/micc6ppt_files/slide0004_image012.jpghttp://en.wikipedia.org/wiki/AIDS http://www.med.wayne.edu/immunology/department/roberts2.html
HIV budding from a cultured lymphocyte
Budding Influenza Virus
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Viral Pathogenesis• Interaction between the virus and the host
• General Steps:
• Entry into the body (ex. Fecal-Oral, Inhalation)
• Primary Site of Replication
• Viremia
• Secondary Site of Replication in target tissues
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Example: Ebola
Primary Target
Secondary Targets
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Outcomes of Virus Infection at the Cellular Level
• Failed infection (abortive)
• Cell death:• Lytic viruses• Apoptosis (programmed cell death)
• Infection without cell death
• Chronic infection: no cell lysis, new viruses are produced
• Latent infection: limited production of viral components; no new viruses produced
• Cellular properties may change later resulting in viral production (ex. Herpes Simplex Virus)
• Transformation: Virus infection results in cell immortalization (conversion to a tumor cell)
• Oncogenic viruses
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Host Defenses Against Viruses• Natural Barriers of the Body (ex. Skin)
• Innate Immune Defenses (not antigen dependent)• Interferon response• Macrophages• Dendritic cells• Natural Killer Cells
• Antigen-specific immune responses• Antibodies• Helper T-cells
• Cell-mediated immunity• Recognition of virus-infected cells• Lysis of infected cells
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Viral Strategies to Evade Host Defenses
• Preventing interferon action:• Presence of double-stranded RNA in cell causes interferon response
• Shuts down cellular translation (suspended animation)
• Degradation of viral RNA
• Changing viral antigens• High error-rate in many viral polymerases• Allows rapid change of protein sequences and, therefore, antigenic characteristics
• Cell-to-cell spread: Evade antibodies
• Suppression of antigen presentation and lymphocyte function (hide from immune system)
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Viral immunopathogenesisImmunopathogenesis Immune Mediators Examples
Flulike symptoms Interferon, cytokines Respiratory viruses, arboviruses (viremia-inducing viruses)
Delayed-type hypersensitivity and inflammation
T cells, macrophages, and polymorphonuclear leukocytes
Enveloped viruses
Immune complex disease Antibody, complement Hepatitis B virus, rubella
Hemorrhagic disease T cell, antibody, complement
Yellow fever, dengue, Lassa fever, Ebola viruses
Postinfection cytolysis T cells Enveloped viruses (e.g., postmeasles encephalitis)
Immunosuppression - Human immunodeficiency virus, cytomegalovirus, measles virus, influenza virus