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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)
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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
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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
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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
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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
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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).
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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.
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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
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Recombination
In DNA and
RNA viruses
Reassortment
occurs only in segmented RNA
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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
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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
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II. Non genetic Interaction.
1- Heterozygosis
2- Phenotypic mixing
3- Interference
Non genetic interaction
Polypoidy Hetroypoidy Phenotypic mixing
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Impacts of studying viral genetics
Gene therapy: retroviruses and adenoviruses
Gene marker vaccine: Herpes
Cold adapted vaccine: Influenza
Others
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