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I. Viral Genomes
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9.1 Size and Structure of Viral Genomes
• Viral genome size (Figure 9.1)
• Smallest circovirus: 1.75-kilobase single strand
• Largest megavirus: 1.25-megabase pairs
• Viral genomes (Figure 9.2)
• Either DNA or RNA genomes
• Some are circular, but most are linear
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Figure 9.1
9.1 Size and Structure of Viral Genomes
• Classification
Based mainly on idea proposed by David
Baltimore (Baltimore Scheme)
• Depends on relationship of genome to mRNA
• Genome structure is the key feature
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Transcription
Genome
replication
Class I & VII
dsDNA (±) virus
Class II
ssDNA (+) virus
Class III
dsRNA (±) virus
Class IV
ssRNA (+) virus
Class V
ssRNA (–) virus
Class VI
ssRNA (+) retrovirus
Transcription of
the minus strand
Synthesis of the
minus strand
Transcription of
the minus strand
Used directly
as mRNA
Transcription of
the minus strand
Reverse
transcription
dsDNA intermediate
dsDNA intermediate
(replicative form)
mRNA (+)
DNA Viruses
RNA Viruses
Class I classical semiconservative
Class II classical semiconservative,
discard (–) strand
Class VII transcription followed by
reverse transcription
Class
Class
Class
Class
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Transcription of
the minus strand
III make ssRNA (+) and transcribe from this to give ssRNA (–) complementary strand
IV make ssRNA (–) and transcribe from this to give ssRNA (+) genome
V make ssRNA (+) and transcribe from this to give ssRNA (–) genome
VI make ssRNA (+) genome by transcription of (–) strand of dsDNA
Figure 9.2
II. Viruses with DNA Genomes
• 9.6 Uniquely Replicating DNA Animal Viruses
• 9.7 DNA Tumor Viruses
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9.6 Uniquely Replicating DNA Animal Viruses
• Double-stranded DNA animal viruses that have
unusual replication strategies
• Pox viruses
• Adenoviruses
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9.6 Uniquely Replicating DNA Animal Viruses
• Pox viruses
• Among the most complex and largest animal viruses
known (Figure 9.11)
• Variola virus (Smallpox virus) most famous
• Vaccinia virus in lab, other pox viruses in nature
• DNA replicates in the cytoplasm
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Pox viruses are ds
DNA
Viruses that replicate
in
The cytoplasm
What do they need to do this?
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9.6 Uniquely Replicating DNA Animal Viruses
• Adenoviruses
• Major group of icosahedral, linear, double-stranded
DNA viruses
• Cause mild respiratory infections in humans
• DNA replicates in the nucleus
• Replication requires protein primers and avoids synthesis
of a lagging strand (Figure 9.12)
• Two unusual characteristics
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Terminal
protein 5′
3′
Adenovirus DNA
C
+
–
C
3′
5′
C
3′
5′
Plus strand
is copied.
5′
3′
C
–
+
–
C
5′
3′
3′
C
+
–
–
C
C
Direction of
cyclization
–
3′
5′
3′
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5′
C
Minus strand
is copied.
–
5′
5′
3′
C
5′
5′
Minus strand cyclizes
via inverted terminal
repeats.
–
5′
3′
New
synthesis
leading
strand
5′
C
C
C
+
New
synthesis
leading
strand
+
–
Completed linear
double strand
C
3′
5′
Figure 9.12
• Covalently linked
protein TP
• pTP is primer
• Strand displacement
replication
• Viral proteins
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9.7 DNA Tumor Viruses
• Some DNA viruses can induce cancer (“tumor
viruses or “oncoviruses”
• Human Papilloma Viruses (HPV)
• Herpesviruses
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9.7 DNA Tumor Viruses
• HPV
• Nonenveloped icosahedral virionNo enzymes in the
virion; replicates in host nucleus
• Basal skin cells
• 8 kbp DNA is circular (Figure 9.13a)
• Small genome, has overlapping genes
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9.7 DNA Tumor Viruses
• Some papilloma viruses cause cancer
• In most infected host cells, virus infection results in the
formation of new virions and the release from host cell
• In a few infected host cells, the virus DNA becomes
integrated into host DNA (analogous to a prophage),
genetically altering cells in the process (Figure 9.13b)
• Integrated virus DNA can inactivate cellular tumor
suppressor genes or express its own tumor activator
genes
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Infection
Tumor virus DNA
+
Host DNA
Viral DNA
Viral DNA integrates
into host DNA.
Transcription of
tumor-inducing genes
Tumor virus mRNA
Transport of mRNA to
cytoplasm and translation
Viral
tumor-induction
proteins
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Transformation of
cell to tumor state
Figure 9.13b
9.7 DNA Tumor Viruses
• Herpesviruses
• Large group of viruses that cause diseases in humans
and animals
• Initial infection may be symptomatic or asymptomatic
• Virus remains hidden or “latent” for extended periods of
time
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9.7 DNA Tumor Viruses
• Some Herpesviruses cause cancer
• Epstein-Barr Virus
• HHV-8
• Diverse mechanisms
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III. Viruses with RNA Genomes
• 9.11 Viruses That Use Reverse Transcriptase
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9.11 Viruses That Use Reverse Transcriptase
• Retroviruses (RNA viruses) and hepadnaviruses
(DNA viruses) use reverse transcriptase for
replication
• Key first step in virus replication cycle
• Reverse Transcriptase
• Enzyme activity that converts ss RNA into ds DNA
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9.11 Viruses That Use Reverse Transcriptase
• Retroviruses (cont'd)
• Genome RNA reverse transcribed to dsDNA
• Inserts into chromosome
• Provirus
• Gene expression and protein processing are complex
(Figure 9.22)
• Gag, pol, env gene regions common to all retroviruses
• Retroviruses that cause cancer often have an extra
gene region “src”
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RNA tumor virus genome
• Src is an “oncogene”
• C-src = normal cellular version
• V-src = version carried by virus
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© 2015 Pearson Education, Inc.
© 2015 Pearson Education, Inc.
© 2015 Pearson Education, Inc.
9.11 Viruses That Use Reverse Transcriptase
• Hepadnaviruses
• Virions small, irregular-shaped particles (Figure 9.23a)
• Include hepatitis B
• Can lead to liver cancer
• Viral replication occurs through an RNA intermediate
• Unusual genomes
• Tiny
• Only partially double-stranded (Figure 9.23b)
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IV. Subviral Agents
• 9.12 Viroids
• 9.13 Prions
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9.12 Viroids
• Viroids: infectious RNA molecules that lack a protein coat
• Smallest known pathogens (246–399 bp)
• Cause a number of important plant diseases
(Figure 9.24)
• Small, circular, ssRNA molecules (Figure 9.25)
• Do not encode proteins; completely dependent on
host-encoded enzymes
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9.13 Prions
• Prions: infectious proteins whose extracellular
form contains no nucleic acid
• Known to cause disease in animals (transmissible
spongiform encephalopathies)
• Host cell contains gene (PrnP) that encodes native form
of prion protein that is found in healthy animals
(Figure 9.27)
• Prion misfolding results in neurological symptoms of
disease (e.g., resistance to proteases, insolubility, and
aggregation)
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Neuronal cell
Prnp
Nucleus
DNA
Transcription
Translation
Normal
function
PrPc
(normal
prion)
PrPSc-induced
misfolding of PrPC
Abnormal
function
PrPSc
(misfolded prion)
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Figure 9.27
Chronic Wasting Disease in deer and elk
Mad Cow Disease
Kuru, KJD in humans
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