week 6 viral genetic october 2013.pdf

8/10/2019 WEEK 6 Viral genetic October 2013.pdf

1/14

/ /

Viral Genetics

Ahmed Sayed Abdel-Moneim

Professor of Virology- College of Medicine, Taif

University, SA

Selected Reading

Cann Principles of Molecular Virology 4th ed

Fundemntal Virology (Fields)
http://www.pdfcomplete.com/cms/hppl/tabid/108/Default.aspx?r=q8b3uige22http://www.pdfcomplete.com/cms/hppl/tabid/108/Default.aspx?r=q8b3uige22http://www.pdfcomplete.com/cms/hppl/tabid/108/Default.aspx?r=q8b3uige22http://www.pdfcomplete.com/cms/hppl/tabid/108/Default.aspx?r=q8b3uige22http://www.pdfcomplete.com/cms/hppl/tabid/108/Default.aspx?r=q8b3uige22http://www.pdfcomplete.com/cms/hppl/tabid/108/Default.aspx?r=q8b3uige22


2/14

/ /

Learning objectives

To know different types of viral mutation

To know how viruses mutate

To know different virus phenotypes and the

significance of each of them.

Different types of viral genetics and non genetic

interaction

Impact of viral genetics on humanities

MutagenesisA-Spontaneous

B-InducedChemical deaminating agents: nitrous acid alkylating agents: nitrosoguanine

base analog: 5 bromouracil

intercalating agents: acrydine orange

PhysicalUV Radiation


3/14

/ /

Type of mutation

Point mutation: base substitution1. Silent mutation

5AUG UUU ACA AAA CUG UAA 3

met- phe- thr- lys- leu- COOH

5AUG UUU ACC AAA CUG UAA 3

met- phe- thr- lys- leu- COOH


4/14

/ /

Point mutation2. Non silent- mutation

5AUG UUU ACA AAA UAA 3

met-phe-thr- lys-COOH

5AUG UUU AUA AAA UAA 3

met-phe-Ile- lys-COOH


5/14

/ /

Point mutation3. Nonsense mutation

5AUG UUU AUA AAA CUC UAA 3

met- phe- Ile- lys- leu- COOH

5AUG UUU AUA UAA CUC UAA 3

met- phe- Ile-COOH

Fame shift mutation

1. Insertion

5AUG UUU CUC AUC ACC 3

met- phe- leu- Ile- thr

5AUG AUU UCU CAU CAC 3

met- Ile- Ser- His- His


6/14

/ /

Frame shift mutation2. Deletion

5AUG UUU CUC AUC ACC 3

met- phe- leu- Ile- thr

5AUG UUC UCA UCA CC 3

met- phe- ser- ser-

Suppression The effect of the suppressor mutation is to by pass the defect

of the original mutation and restore the wild phenotype to avirus with a mutant phenotype .

a) Intragenic suppression

A suppressor mutation may occur at a second site in the samegene as the original mutation

b) Extragenic suppression

A suppressor mutation in a gene different from thegene containing the original mutation (extragenicsuppression).


7/14

/ /

Change in phenotypicexpression

1. Plaque morphology mutation

It occurs due to metabolic differences between mutant andwild type virus ex. plaques formed by adenovirus mutant arelarge in size than that produced by wild type one.

2. Temperature sensitive (ts) mutation

A conditional mutation in which the viral mutant is ableto replicate at a temperature range but not at another,the parent(wild type) strain being able to replicate over the wholetemperature range (37-40C).

The mutant phenotype in one (restrictive or non-permissive)temperature range and the wild-type phenotype in another

(permissive) temperature range.3- Hot adapted mutation :

Hot mutant can grow well at temperature higher than needed bywild-type virus. Such mutants are very virulent, since they canmultiply rapidly in patients with higher fever.

4- Cold - adapted mutation :

These mutants are unable to grow at high temperature.


8/14

/ /

5- Host range mutation :

Sometime the wild type virus has the ability to grow indifferent hosts cells but a mutation may lead to viruses growonly in selected hosts. eg. Rabbit adapted rabies virus

6- Drug- resistant mutation :

Certain drugs are capable of inhibiting the multiplication ofcertain viruses, but some mutants are resistant to thesedrugs.

Interaction Between Viruses

I. Genetic interaction

1- Recombination

2- Reassortment

3- Complementation

II. Non genetic Interaction.

1- Heterozygosis

2- Phenotypic mixing

3- Interference


9/14

/ /

Recombination

In DNA and

RNA viruses

Reassortment

occurs only in segmented RNA


10/14

/ /

Mutation by antigen shiftingInfluenza Type A

A novel HA or NA subtype from

avian genome is incorporated in

an existing virus genome.

A new subtype is born,

which may have pandemic

potential

Influenza viruses are genetically

changed in vigour

Antigenic drift [Point mutaion(s)]:

It is a change in the viral genetic material that affect

epitope configuration and leads to virus escape from

the neutralizing antibodies.

Antigenic shift [Reassortment ]

It occurs only in segmented RNA


11/14

/ /

RNARNA

HemagglutininHemagglutinin

NeuraminidaseNeuraminidase

AntibodiesAntibodies

Sialic acidSialic acid

DriftChange in the epitope configuration

Complementation

It occurred when two viruses , one considered as defective in some gene product and the

second is not, replicate in an infected cell that results in the yield of one or both parental

mutants being enhanced while their genotypes remained unchanged

Two types of complementation was found between viruses :

Intragenic complementation:

where different mutants have complementing defects in the same protein.

Intergenic [Extragenic] complementation:

resulting from mutants with defects in different genes


12/14

/ /

II. Non genetic Interaction.

1- Heterozygosis

2- Phenotypic mixing

3- Interference

Non genetic interaction

Polypoidy Hetroypoidy Phenotypic mixing


13/14


14/14

/ /

Impacts of studying viral genetics

Gene therapy: retroviruses and adenoviruses

Gene marker vaccine: Herpes

Cold adapted vaccine: Influenza

Others

week 6 viral genetic october 2013.pdf

Documents