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] Viral replication: How viruses exploit cells to make new viruses.
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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
• 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)