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Viral Genetics. Hsiao-Sheng Liu 劉校生 國立成功大學微生物暨免疫學研究所. The objectives. What kind of genetic changes are detected in viruses? The effects of viral genetic changes on viral virulence The application of viral mutants. What kind of genetic changes are detected in the virus?. A. Mutation
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Viral Genetics Hsiao-Sheng Liu劉校生國立成功大學微生物暨免疫學研究所
The objectives • What kind of genetic changes are detected in viruses? • The effects of viral genetic changes on viral virulence • The application of viral mutants
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
A.Mutation B. Recombination (Reassortment)
HA NA HA NA Attenuated virus Violent virus Hemagglutinin HA NA Neuraminidase Lipid bilayer Ribonucleoprotein Matrix protein Recombinant virus
Antigen drift: gene mutation • Antigen shift: gene recombination
Antigen Antigen
NP: nucleoprotein Mutation Recombination
Mutation Recombination (Reassortment) C. Transcapsidation: Phenotype of A and genome of B D. Marker rescue
Molecular analyses by RT-PCR: @ A 405 nucleotide segment of the coronavirus polymerase gene was amplified.
Mutants • Lethal mutant • Plaque mutant • Host-range mutant • Attenuated mutant • Temperature sensitive mutant
What is the application of viral mutants? Vaccine Understanding a mutated virus is the first step to find a vaccine
1. Rapidly amplified in appropriate cell 2. Deliver the gene without producing infectious virus
Virus-mediated gene transfer in mammalian cells 1. Retrovirus 2. Adenovirus 3. Adenovirus-associated virus 4. Herpes simplex virus
A. Defective Interfering viral particle (DI) B. Pseudovirion: Virus particle contains host nucleic acid
Web site for virology • General virology: www.tulane.edu/~dmsander/garryfavweb.html • Taxonomy of viruses: life.anu.edu.au/viruses/Ictv/index.html • Infectious diseases: www.gen.emory.edu/medweb/medweb.id.html
H1N1 H5N1