1. Viral Genetics

2. Introduction The terms mutant, strain, type, variant and even
isolate have all been used extensively and rather
loosely without discrimination.
All of these terms were used to designate a virus
that differs in some inheritable way from a parental
or wild virus.
It is now recognized that what is designated wild
type may not accurately reflect the nature of a virus
or a gene as it is isolated from nature (field isolate).

3. Wild Type
It is an arbitrary designation that has a narrow connotation, used to designate the original, usually laboratory- adapted strain of a virus from which mutants are selected and to which those mutants are compared.
Strain
It is often used to designate different wild types of the same virus (isolated from different geographical locations or patients).

4. Type
It has come to be synonymous with serotype
as determined by neutralization of infectivity.
Variant
It is generally used to indicate a virus that is phenotypically different from the wild type but for which the genotypic basis of the variation is unknown.

5. Genetically, Viruses have many features
in common with cells:
Viruses are subject to mutations.
The genomes of different viruses can recombine to form novel progeny.
The expression of the viral genome can be regulated.
Viral gene products can interact.

6. Regarding genetic variation in viruses, two
principal mechanisms are involved:-
Mutation
Recombination
Such variation may lead to the emergence
of new viral serotypes or viruses of
altered virulence.

7. Spontaneous Mutation
Spontaneous mutations accumulate in the genomes of viruses and induce the variation in phenotype that is subjected to selection pressure during the evolution of a virus.
The rates of spontaneous mutation can be as low as 10-8 to per incorporated nucleotides in DNA genomes.
In viruses with RNA genomes, higher rates of spontaneous mutations have been measured, in the order of 10-3 to 10-4 per incorporated nucleotides

8. While the genomes of DNA viruses are relatively stable, the high rates of spontaneous mutation in RNA genomes suggest that the concept of wild type is very fleeting in RNA genome systems.
However, wild type RNA viruses replicate more rapidly than mutants dominating population, but other factors operate to favor the accumulation of mutants in a virus population (difficulty in production of genetically homogenous high- titer virus stocks).

9. Types of Mutation Null mutation Temperature- Sensitive Mutation
Cold-sensitive mutation
Plaque- morphology Mutation
Host-Range Mutations

10. Types of Mutation…cont’d
Antibody Escape / Resistance Mutation
Revertants, Suppressors, and Heterozygosis
Lethal Mutations
Deletion mutations
Attenuated Mutations

11. Mutations in essential genes inactivate the virus, but mutations in other genes can produce antiviral drug resistance or alter the antigenicity or pathogencity of the virus.
Not all mutations that occur persist in the virus population. Mutations that interfere with the essential functions of attachment, penetration, uncoating, replication, assembly and release do not permit multiplication and are rapidly lost from the population.

12. However, because of the redundancy of the genetic code, many mutations are neutral, resulting either in no change in the viral protein or in replacement of an amino acid by a functionally similar amino acid.
Only mutations that do not cripple essential viral functions can persist or become fixed in a virus population.

13. Virus-Virus Interactions
Virus–Virus and Virus–Host interactions that Affect Phenotype and genotype
Virus-Virus Interactions
A- Phenotypically
Pyenotypic Mixing:-
- Capsid derived from both viruses
- Transcapsidation and pseudotype formation
Interference
Autointerference
Homologous interference
Heterologous interference

14. Complementation Mechanisms of interference :
1- Blocking of receptor ( inhibition of adsorption).
2- Competition for components of the replicative
apparatus (sites and/ or substrates).
3- Inhibitors of replication (interferon).
Significance in natural infections, polyvalent vaccination and vaccine and infection.
Complementation

15. B- Genotypic Interactions
1- Recombination
2- Genetic Reactivation
a- Marker rescue
b- Multiplicity Reactivation
Mechanisms
Independent reassortment (multipartite RNA viruses)
Incompletely linked genes ( DNA, RNA viruses).
- break –rejoin mechanism (DNA viruses)
- copy- choice mechanism (RNA viruses)

16. Recombination by independent assortment during dual infection

17. Recombination by break-rejoin of incompletely linked genes

18. Recombination by copy-choice of incompletely linked genes