Genetic changes in

viral genome

Mousumi Bora
P-1893
Division of Virology
IVRI
 Contents

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Introduction
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• Engage your Audience
Types of genetic
• Capture changes
Audience in viral genome
Attention

Mechanism of acquiring mutations

 Introduction

• Viruses grow rapidly, there are usually a large number

of progeny virions per cell

• More chance of mutations occurring over a short time

period

• The nature of the viral genome (RNA or DNA;

segmented or non-segmented) plays an important role in
the genetics of the virus
The Central Dogma of Cell Biology
 Genetic changes in the viral genome

• Random mutation
1

• Recombination
2
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• Reassortment
• Using
3 Awesome Backgrounds

• Engage
4
your amplification/reduction
• Gene Audience
• Capture Audience Attention
• Quasispecies
5

• Defective interfering genomes

6

7
• Reactivation

8
• Phenotypic mixing
 Mutation
• Any change to the Nitrogen Bases in DNA are called
mutations
 Change the DNA

 Changes the mRNA

 May change protein

 May change trait

 Types of mutation
A. Single nucleotide replacement :
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Missense

Nonsense

Silent
 Types of mutation cont..
B. Insertion/deletion of nucleotides
Insertions are mutations in which extra base pairs are
inserted into a new place in the DNA

Deletions are mutations in which a section of DNA is lost, or

deleted
 Types of mutation cont..

C. Frameshift mutation : Since protein-coding DNA is

divided into codons three bases long, insertions and
deletions can alter a gene so that its message is no longer
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 Types of mutation cont..
D. Inversion: DNA sequence of nucleotides is reversed.
Inversions can occur among a few bases within a gene
or among longer DNA sequences that contain several
genes
 Recombination

1 • Classic recombination
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• 2
Engage your • Copy choice recombination
Audience
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3 • Site specific recombination

4 • Intramolecular recombination
 A. Classic recombination

• Involves breaking of Common in DNA

covalent bonds viruses
• Exchange of genetic
information
• Reforming of covalent
bonds
• Common in DNA viruses
and Retroviruses
• Coronaviruses
• Picornaviruses
 B. Copy choice recombination
• A genetic recombination mechanism where the new DNA
molecule comes about by replicating selected parts of
each parental DNA molecule and by alternating between
the two
• Observed in Retroviruses

• Recombination occurs as the single-strand (+)RNA

genomes are reverse transcribed to form DNA

• During reverse transcription the nascent DNA can switch

multiple times between the two copies of the viral RNA

• Rapidly shuffle the genetic information that is transmitted

from parental to progeny genomes
 B. Copy choice recombination cont..

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 C. Site specific recombination
•Site-specific recombination moves specialized nucleotide
sequences, called mobile genetic elements, between non-
homologous sites within a genome

•The movement can occur between two different positions in a

single chromosome, as well as between two different
chromosome

•Mechanism of site specific recombination requires specialized

recombination enzymes and specific DNA sites

1 • Tranpositional SSR

2 • Conservative SSR
 Tranpositional SSR
• Usually involves breakage reactions at the ends of the mobile DNA
segments embedded in chromosomes and the attachment of those ends
at one of many non homologous target DNA sites
• Does not involve the formation of heteroduplex DNA
 Tranpositional SSR cont..
• Transpositional site-specific recombination by a retrovirus or a
retroviral-like retrotransposon
 Conservative SSR
• Involves the production of a very short heteroduplex joint

• Requires a short DNA sequence that is the same on both

donor and recipient DNA molecules
 D. Intra molecular recombination

•Involves the exchange of nucleotide sequences

between different but closely related viruses during
replication
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••Occurs
Engagemostly
your Audience
in dsDNA viruses because of template
•switching
Captureby viral DNAAttention
Audience polymerase

•Adeno, Hepadna, Polyomaviruses

D. Intra molecular recombination cont..
D. Intra molecular recombination cont..
 Reassortment

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Reassortment cont..
Reassortment cont..
 Gene amplification/reduction

• A multistep process of gene amplification, mutation, and

reduction allows different viruses to overcome host antiviral
defenses

• Adaptation starts with spontaneous formation of a wide

variety of gene duplications

• Poxviruses
 Gene amplification/reduction cont..

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 Viral Quasispecies

• A viral quasispecies is a group of viruses related by a

similar mutation or mutations, competing within a highly
mutagenic environment
influenced

• The long-term evolution of the virus better

evolutionarily stable strategy to generate a broad
quasispecies with members of approximately equal
fitness than to have a sharply defined 'most fit' single
genotype

• This has been called 'survival of the flattest'

 Viral Quasispecies cont..

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 Defective interfering genome
• Spontaneously generated virus mutants in which a critical
portion of the particle's genome has been lost due to
defective replication

• Need the presence of parental wildtype virus

• At the same time they interfere and decreases the yield of

the parental virus

• DI particles of RNA viruses – Deletion mutants

• Influenza, Reoviruses
 Reactivation

• Cell infected with two or more viruses of the same strain

that have suffered a lethal mutation in different gene
results in production of infectious progeny

• Reactivation/ Multiple reactivation

• Herpes simplex virus, Varicella zoster virus, Epstein-Barr

virus, Human cytomegalovirus, HHV6, HHV7, Kaposi's
sarcoma-associated herpesvirus, JC virus, Parvovirus
and Adenovirus
 Phenotypic mixing

• Two viruses when co-infect the same cell

• Progeny virions acquire the phenotypic characterstics from

both the parents

• Cells co-infected with Influenza and a Paramyxovirus, the

envelope of some of the progeny particles display antigens
derived from both the parents
Phenotypic mixing
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