Genetic changes in viral genome

Mousumi BoraP-1893

Division of VirologyIVRI

Contents

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Introduction

Types of genetic changes in viral genome

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

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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

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 mutationA. Single nucleotide replacement : • Engage your Audience• Capture Audience Attention

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..

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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

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

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1 • Classic recombination

2 • Copy choice recombination

3 • Site specific recombination

4 • Intramolecular recombination

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

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

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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

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

• 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

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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