Genetic mutations in the viral genome

1. Genetic changes in
viral genome
Mousumi Bora
P-1893
Division of Virology
IVRI

2. Contents
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Introduction
Types of genetic changes in viral genome
Mechanism of acquiring mutations

3. 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

4. The Central Dogma of Cell Biology

5. Genetic changes in the viral genome
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1
• Random mutation
2
• Recombination
3
• Reassortment
4
• Gene amplification/reduction
5
• Quasispecies
6
• Defective interfering genomes
7
• Reactivation
8
• Phenotypic mixing

6. Mutation
• Any change to the Nitrogen Bases in DNA are called
mutations
 Change the DNA
 Changes the mRNA
 May change protein
 May change trait

7. Types of mutation
A. Single nucleotide replacement :
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Missense
Nonsense
Silent

8. 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

9. Types of mutation cont..
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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
correctly parsed

10. 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

11. Recombination
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• Classic recombination1
• Copy choice recombination2
• Site specific recombination3
• Intramolecular recombination4

12. A. Classic recombination
• Involves breaking of
covalent bonds
• Exchange of genetic
information
• Reforming of covalent
bonds
• Common in DNA viruses
and Retroviruses
• Coronaviruses
• Picornaviruses
Common in DNA
viruses

13. 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

14. B. Copy choice recombination cont..
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15. 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
• Tranpositional SSR1
• Conservative SSR2

16. 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

17. Tranpositional SSR cont..
• Transpositional site-specific recombination by a retrovirus or a
retroviral-like retrotransposon

18. 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

19. D. Intra molecular recombination
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•Involves the exchange of nucleotide sequences
between different but closely related viruses during
replication
•Occurs mostly in dsDNA viruses because of template
switching by viral DNA polymerase
•Adeno, Hepadna, Polyomaviruses

20. D. Intra molecular recombination cont..

21. D. Intra molecular recombination cont..

22. Reassortment
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23. Reassortment cont..

24. Reassortment cont..

25. 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

26. Gene amplification/reduction cont..
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27. Viral Quasispecies
• A viral quasispecies is a group of viruses related by a
similar mutation or mutations, competing within a highly
mutagenic environment
• 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'
influenced

28. Viral Quasispecies cont..
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29. 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

30. 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

31. 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

32. Phenotypic mixing

33. THANK YOU