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Page 1: Viral Genetics

Viral GeneticsHsiao-Sheng Liu 劉校生 國立成功大學微生物暨免疫學研究所

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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

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What kind of genetic changes are detected in 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 HA NANA

HA NAHemagglutinin

NeuraminidaseLipid bilayer

Matrix proteinRibonucleoprotein

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• Antigen drift: gene mutation

• Antigen shift: gene recombination

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Antig

en

Antige

n

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• NP: nucleoprotein

Mutation Recombination

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A. MutationB. 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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From Times

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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 cells1. Retrovirus2. Adenovirus3. Adenovirus-associated virus4. 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/garryfavweb.html

• Taxonomy of viruses: life.anu.edu.au/viruses/Ictv/index.html

• Infectious diseases: www.gen.emory.edu/medweb/medweb.id.html

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Genetic change between viral particles

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H5N1

H1N1


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