LECTURE 2 REPLICATION OF VIRUSES 2010-2011 · structure of the virus particle is formed. ... In most viruse the antigenicity is ... LECTURE 2 REPLICATION OF VIRUSES 2010-2011

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Replicative cycle

� As obligate intracellular parasites, Virus must enter and replicate in living cells in order to “reproduce” themselves. This “growth cycle” involves specific attachment of virus, penetration and uncoating, nucleic acid transcription, protein synthesis, maturation and assembly of the virions and their subsequent release from the cell by budding or lysis

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Attachment/Adsorption

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Attachment/Adsorption

Attachment/AdsorptionVirus Target Cell Receptor

Epstein-Barr virus B lymphocyte CR2 (CD21) receptor (complement)

Human immunodeficiency virus

T lymphocyte CD4 molecule and chemokinecoreceptors

Rhinovirus Epithelial cells ICAM-1 (protein from immunoglobulin superfamily)

Poliovirus Epithelial cells protein from immunoglobulin superfamily

Rabies virus Nerve cells acetyl choline receptor

Influenza A Epithelial cells Sialic acid

B19 parvovirus Erythroid precursor cells

Erythrocyte P antigen (globozid)

PENETRATION(Virus enters the cell)

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Fusing

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Fusing

13herpesviruses, paramyxoviruses, HIV

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Endocytosis

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Enveloped viruses

� Some enveloped viruses require an acid pH for fusion to occur and are unable to fuse directly with the plasma membrane. These viruses are taken up by invagination of clathrin coated pits into endosomes. As the endosomes become acidified, the latent fusion activity of the virus proteins becomes activated by the fall in pH and the virion membrane fuses with the endosome membrane. This results in delivery of the internal components of the virus to the cytoplasm of the cell

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Non-enveloped viruses

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UNCOATING

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BIOSYNTHESIS

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The Baltimore classification system

Based on genetic contents and replication strategies of viruses, viruses are divided into the following seven classes:

1. dsDNA viruses2. ssDNA viruses 3. dsRNA viruses 4. (+) sense ssRNA viruses (codes

directly for protein) 5. (-) sense ssRNA viruses 6. RNA reverse transcribing viruses7. DNA reverse transcribing viruses


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ssDNAIncompletessDNA

dsDNA

mRNA +RNA

+RNA

- RNA

dsRNA

Limits of DNA polymerase III� can only build onto 3′′′′ end of

an existing DNA strand

DNA replication

5′′′′

5′′′′

5′′′′

5′′′′

3′′′′

3′′′′

3′′′′

5′′′′3′′′′

5′′′′3′′′′ 3′′′′

Leading strand

Lagging strand

Okazaki fragments

ligase

Okazaki

Leading strand� continuous synthesis

Lagging strand� Okazaki fragments� joined by ligase

DNA polymerase III

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3′′′′

5′′′′

growing replication fork

DNA polymerase III

RNA primer� serves as starter sequence

for DNA polymerase III

5′′′′

5′′′′

5′′′′

3′′′′

3′′′′

3′′′′

5′′′′

3′′′′ 5′′′′3′′′′ 5′′′′ 3′′′′


RNA

DNA replication

DNA polymerase I� removes sections of

RNA primer and replaces with DNA nucleotides

5′′′′

5′′′′

5′′′′

5′′′′

3′′′′

3′′′′

3′′′′

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DNA polymerase I

RNA

ligase

DNA replication

3’ 5’

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3’ 5’

5’ 3’

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RNA replication

mRNA ProcessingmRNA ProcessingDNADNA

Add 5Add 5’’ capcap

Remove Remove IntronsIntronsSplice Splice ExonsExons

together together

Cleave at 3Cleave at 3’’ endendAdd 3Add 3’’ polypoly--A tailA tail

Transcription Transcription

Pre mRNAPre mRNA

Mature mRNA leaves for cytoplasmMature mRNA leaves for cytoplasm

In nucleusIn nucleus

55’’ 33’’intronintron 11 intronintron 22ExonExon 11 ExonExon 22 ExonExon 33

m7m7GG--PP--PP--PP--intronintron 11 intronintron 22ExonExon 11 ExonExon 22 ExonExon 33

AAAAAAAAAAAA……....m7m7GG--PP--PP--PP--intronintron 11 intronintron 22ExonExon 11 ExonExon 22 ExonExon 33

AAAAAAAAAAAA…………m7m7GG--PP--PP--PP--ExonExon 11 ExonExon 22 ExonExon 33

Start Codon

Stop Codon

ProteinProtein--coding Regioncoding Region


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Flow of events - replication of herpesviruses

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Adsorption

Penetration

Decapsidation

Conversion to dsDNA

Transcription

Translation

Genome replication

Assembly

Release

Flow of events - replication of parvoviruses

Nucleus

Viral Proteins

mRNA


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Flow of events - replication of reovirusesAdsorption and penetration

Adsorption and penetration

Transcription

Translation

Late transcription and translation

Provirus assembly

Assembly

Release

mRNA

Nucleus


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Flow of events - replication of picornavirusesAdsorption and penetration

Decapsidation

Translation

Cleavage of poliprotein

Genome replication

Assembly and release

Nucleus

polymerase


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Flow of events - replication of orthomyxoviruses

Adsorption

Penetration

DecapsidationTranscription

TranslationGenome replication

Assembly

Release

(5’cap-mRNA-polyA)10

((+)RNA)8

Nucleus


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Flow of events - replication of retrovirusesAdsorption

Penetration Incomplete decapsidation

Reverse transcription

Integration of proviral dsDNA

Transcription

Translation

Genome replication

Protein glycolization

Assembly

Release

Maturation

Protein glycolization

Nucleus


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Flow of events - replication of Hepadnaviruses

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Maturation

� The stage of viral replication at which a virus particle becomes infectious; nucleic acids and capsids are assembled together.

ASSEMBLY

� The stage of replication during which all the structural components come together at one site in the cell and the basic structure of the virus particle is formed.

RELEASE

� Disintegration : naked virus cause the host cell lysis

� Budding: enveloped viruses� Budding viruses do not necessarily kill the

cell. Thus, some budding viruses may be able to set up persistence

RELEASE

Cell lysisBudding

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There are two important variation which relate well with medical practices

� Antigenicity variation: In most viruse the antigenicity is stable but in some viruses such as influenze virus the antigenicity may vary and cause the disease to epidemic.

� Virulence variation(Virulent viruses): Less virulent viruses always used in prevention.

LECTURE 2 REPLICATION OF VIRUSES 2010-2011 · structure of the virus particle is formed. ... In most viruse the antigenicity is ... LECTURE 2 REPLICATION OF VIRUSES 2010-2011

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