Transcript Viral Genetics

Viral Genetics
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).
 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).
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.
 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.
 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.
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 10-11 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
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 hightiter virus stocks).
Types of Mutation
Null mutation
Temperature- Sensitive Mutation
Cold-sensitive mutation
Plaque- morphology Mutation
Host-Range Mutations
Types of Mutation…cont’d
Antibody Escape / Resistance Mutation
Revertants, Suppressors, and
Heterozygosis
Lethal Mutations
Deletion mutations
Attenuated Mutations
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.
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.
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
 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
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)
Recombination by independent
assortment during dual infection
Recombination by break-rejoin of
incompletely linked genes
Recombination by copy-choice of
incompletely linked genes