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
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Introduction to Virology Casey D. Morrow, Ph.D. Department of Cell Biology [email protected]
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 Presentation
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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
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
Basic Components of a Virion
Virus Classification• Size• Morphology• Genome Type (DNA or RNA)• Means of Replication
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
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
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
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
Polyprotein Strategy
Assembly and Release
• Enveloped Viruses: typically exit by budding from the cell
• Naked viruses: typically exit through cell lysis
• Cell-mediated immunity• Recognition of virus-infected cells• Lysis of infected cells
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)