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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

Mutagenesis
A-Spontaneous
B-Induced
Chemical

deaminating agents: nitrous acid

alkylating agents: nitrosoguanine
base analog: 5 bromouracil
intercalating agents: acrydine orange

Physical
UV

Radiation

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Type of mutation
Point mutation: base substitution
1. Silent mutation
5 AUG UUU ACA AAA CUG UAA 3
met- phe- thr- lys- leu- COOH
5 AUG UUU ACC AAA CUG UAA 3
met- phe- thr- lys- leu- COOH

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Point mutation
2. Non silent- mutation
5 AUG UUU ACA AAA UAA 3

met-phe-thr- lys-COOH
5 AUG UUU AUA AAA UAA 3
met-phe-Ile- lys-COOH

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Point mutation

3. Nonsense mutation

5 AUG UUU AUA AAA CUC UAA 3

met- phe- Ile- lys- leu- COOH
5 AUG UUU AUA UAA CUC UAA 3
met- phe- Ile-COOH

Fame shift mutation

1. Insertion
5 AUG UUU CUC AUC ACC 3
met- phe- leu- Ile- thr
5 AUG AUU UCU CAU CAC 3
met- Ile- Ser- His- His

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Frame shift mutation

2. Deletion
5 AUG UUU CUC AUC ACC 3
met- phe- leu- Ile- thr
5 AUG 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 a
virus with a mutant phenotype .
a) Intragenic suppression
A suppressor mutation may occur at a second site in the same
gene as the original mutation

b) Extragenic suppression
A suppressor mutation in a gene different from the
gene containing the original mutation (extragenic
suppression).

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Change in phenotypic
expression
1. Plaque morphology mutation
It occurs due to metabolic differences between mutant and
wild type virus ex. plaques formed by adenovirus mutant are
large in size than that produced by wild type one.

2. Temperature sensitive (ts) mutation

A conditional mutation in which the viral mutant is able
to replicate at a temperature range but not at another,
the parent(wild type) strain being able to replicate over the whole
temperature 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 by
wild-type virus. Such mutants are very virulent, since they can
multiply 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 in
different hosts cells but a mutation may lead to viruses grow
only in selected hosts. eg. Rabbit adapted rabies virus
6- Drug- resistant mutation :
Certain drugs are capable of inhibiting the multiplication of
certain viruses, but some mutants are resistant to these
drugs.

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 shifting Influenza 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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Drift
Change in the epitope configuration
RNA
Hemagglutinin
Neuraminidase
Antibodies
Sialic acid

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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Non genetic interaction

II. Non genetic Interaction.
1- Heterozygosis
2- Phenotypic mixing
3- Interference

Polypoidy

Hetroypoidy

Phenotypic mixing

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Phenotypic mixing/masking
Parents viruses

Phenotypic mixing

Phenotypic masking

Phenotypic masking

genome A:
mixed capid
[Phenotype mixing]

genome B:
contains capid a
[Transcapsidation]

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Impacts of studying viral genetics

Gene therapy: retroviruses and adenoviruses

Gene marker vaccine: Herpes
Cold adapted vaccine: Influenza
Others