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Viral Genetics
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The objectives What genetic changes are detected in viruses? The effects of viral genetic changes on viral virulence. The application of viral mutants
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What may cause genetic changes of the virus?
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A. Mutation – Poor fidelity of viral polymerase RNA-dependent RNA polymerase – RNA virus lack of genetic error- checking mechanism (one error per 1x10 nucleotides) – Rapid replication rate 3
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A. Mutation B. Recombination (Reassortment)
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Attenuated virus Violent virus Recombinant virus HA NA HA NA Hemagglutinin Neuraminidase Lipid bilayer Matrix protein Ribonucleoprotein
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Antigen drift: gene mutation Antigen shift: gene recommbination
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Antigen
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NP: nucleoprotein
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A.Mutation B.Recombination (Reassortment) C. Transcapsidation: Phenotype of A and genome of B D. Marker rescue
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An example of viral genetic changes: SARS
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Molecular analyses by RT-PCR: @ A 405 nucleotide segment of the coronavirus polymerase gene was amplified.
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What kind of viral mutants may be generated?
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Mutants Lethal mutant; Plaque mutant; Host-range mutant; Attenuated mutant; Temperature sensitive mutant
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What is the application of viral mutants? Vaccine Understanding a mutated virus is the first step to find a vaccine
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Why the virus is used for gene therapy?
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1. Rapidly amplified in appropriate cell 2. Deliver the gene without producing infectious virus
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What viruses are used for gene therapy?
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Virus-mediated gene transfer in mammalian cells 1. Retrovirus 2. Adenovirus 3. Adenovirus-associated virus 4. Herpes simplex virus
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What is the defective virus?
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A. Defective Interfering viral particle (DI) B. Pseudovirion: Virus particle contains host nucleic acid
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Web site for virology General virology: www.tulane.edu/~dmsander/garryfavwe b.html Taxonomy of viruses: life.anu.edu.au/viruses/Ictv/index.html Infectious diseases: www.gen.emory.edu/medweb/medweb.i d.html
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Genetic change between viral particles
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H5N1
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