Viral GeneticsHsiao-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– 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)

Attenuated virus Violent virus

Recombinant virus

HA HA NANA

HA NAHemagglutinin

NeuraminidaseLipid bilayer

Matrix proteinRibonucleoprotein

• Antigen drift: gene mutation

• Antigen shift: gene recombination

Antig

en

Antige

n

• NP: nucleoprotein

Mutation Recombination

A. MutationB. Recombination (Reassortment)

C. Transcapsidation: Phenotype of A and genome of B

D. Marker rescue

An example of viral genetic changes: SARS

Molecular analyses by RT-PCR:@ A 405 nucleotide segment of the coronavirus polymerase gene was amplified.

From Times

What kind of viral mutants may be generated?

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

Why the virus is used for gene therapy?

1. Rapidly amplified in appropriate cell

2. Deliver the gene without producing infectious virus

What viruses are used for gene therapy?

Virus-mediated gene transfer in mammalian cells1. Retrovirus2. Adenovirus3. Adenovirus-associated virus4. Herpes simplex virus

What is the defective 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

Genetic change between viral particles

H5N1

H1N1