Download Replication of Viruses

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
Attachment/Adsorption
Attachment/
Adsorption
Attachment/Adsorption
Virus
Target Cell
Receptor
Epstein-Barr virus
B lymphocyte
CR2 (CD21) receptor
(complement)
Human
immunodeficiency
virus
T lymphocyte
CD4 molecule and
chemokine
coreceptors
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
herpesviruses, 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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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 viruses
2. ssDNA viruses
3. dsRNA viruses
4. (+) sense ssRNA viruses (codes
directly for protein)
5. (-) sense ssRNA viruses
6. RNA reverse transcribing viruses
7. DNA reverse transcribing viruses
The Baltimore classification system
Incomplete
ssDNA
ssDNA
+RNA
dsDNA
- RNA
mRNA
dsRNA
+RNA
Okazaki
DNA replication
Limits of DNA polymerase III
can only build onto 3′′ end of
an existing DNA strand
ents
m
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f
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Okaza
3′′
5′′
3′′
5′′
5′′
5′′
3′′
ligase
growing
3′′
replication fork
5′′
5′′
Lagging strand
Leading strand
3′′
Lagging strand
Okazaki fragments
joined by ligase
3′′
5′′
3′′
DNA polymerase III
Leading strand
continuous synthesis
DNA replication
5′′
3′′
3′′
5′′
5′′
3′′
5′′
3′′
5′′
growing
3′′
replication fork
DNA polymerase III
RNA 5′′
RNA primer
serves as starter sequence
for DNA polymerase III
3′′
DNA replication
DNA polymerase I
removes sections of
RNA primer and replaces
with DNA nucleotides
DNA polymerase I
5′′
3′′
3′′
5′′
5′′
ligase
growing
3′′
replication fork
RNA
5′′
3′′
RNA replication
3’
5’
5’
3’
3’
5’
mRNA Processing
DNA
In nucleus
Transcription
Pre mRNA
5’
m7G-P-P-P-
m7G-P-P-P-
Start
Codon
m7G-P-P-P-
Exon 1 intron 1 Exon 2
Exon 1 intron 1 Exon 2
intron 2
3’
Add 5’ cap
Cleave at 3’ end
Add 3’ poly-A tail
intron 2
Protein-coding Region
Exon 2
Exon 3
intron 2
Exon 1 intron 1 Exon 2
Exon 1
Exon 3
Exon 3
Exon 3
AAAAAA…..
Remove Introns
Splice Exons
together
AAAAAA……
Stop
Codon
Mature mRNA leaves for cytoplasm
The Baltimore classification system
Flow of events - replication of herpesviruses
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The Baltimore classification system
Flow of events - replication of parvoviruses
Adsorption
Penetration
Nucleus
Decapsidation
Translation
Conversion to
dsDNA
mRNA
Transcription
Genome
replication
Viral Proteins
Assembly
Release
The Baltimore classification system
Flow of events - replication of reoviruses
Adsorption and
penetration
Adsorption and penetration
mRNA
Late transcription and translation
Nucleus
Translation
Assembly
Release
Transcription
Provirus
assembly
The Baltimore classification system
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Flow of events - replication of picornaviruses
Adsorption and penetration
Nucleus
Decapsidation
Translation
polymerase
Cleavage of
poliprotein
Assembly and release
Genome
replication
The Baltimore classification system
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Flow of events - replication of orthomyxoviruses
Adsorption
Penetration
Transcription
Genome
replication
Decapsidation
(5’cap-mRNA-polyA)10
((+)RNA)8
Translation
Nucleus
Assembly
Release
The Baltimore classification system
Flow of events - replication of retroviruses
Adsorption
Reverse
transcription
Penetration
Incomplete
decapsidation
Translation
Integration of proviral dsDNA
Nucleus
Transcription
Genome replication
Protein
glycolization
Protein
glycolization
Assembly
Maturation
Release
The Baltimore classification system
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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 lysis
Budding
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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.