1. I. Viral Genomes

2. 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

3. Figure 9.1 Comparative genomics.

4. 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

5. Class I & VII
Class II
Class III
Class IV
Class V
Class VI
dsDNA (±) virus
ssDNA (+) virus
dsRNA (±) virus
ssRNA (+) virus
ssRNA (–) virus
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
(replicative form)
dsDNA intermediate
Transcription
mRNA (+)
Transcription of
the minus strand
DNA Viruses
RNA Viruses
Class I classical semiconservative
Class II classical semiconservative,
discard (–) strand
Class VII transcription followed by
reverse transcription
Class III make ssRNA (+) and transcribe from this to give ssRNA (–) complementary strand
Class IV make ssRNA (–) and transcribe from this to give ssRNA (+) genome
Class V make ssRNA (+) and transcribe from this to give ssRNA (–) genome
Class VI make ssRNA (+) genome by transcription of (–) strand of dsDNA
Genome
replication
Figure 9.2 The Baltimore classification of viral genomes.
Figure 9.2

6. II. Viruses with DNA Genomes
9.6 Uniquely Replicating DNA Animal Viruses
9.7 DNA Tumor Viruses

7. 9.6 Uniquely Replicating DNA Animal Viruses
Double-stranded DNA animal viruses that have unusual replication strategies
Pox viruses
Adenoviruses

8. 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

9. Viruses that replicate in The cytoplasm
Pox viruses are ds DNA
Viruses that replicate in
The cytoplasm
Figure 9.11 Smallpox virus.
What do they need to do this?

10. 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

11. Figure 9.12 Figure 9.12 Adenoviruses. Terminal protein Adenovirus DNA5′ C + 3′ 3′ – C 5′
Plus strand
is copied. 5′ C + 3′ 3′ – – C 5′
New
synthesis
leading
strand C 5′ 5′ C + 3′ – C 5′ 3′ – C 5′
Direction of cyclization 3′ – C 5′
Minus strand cyclizes
via inverted terminal
repeats.
Figure 9.12 Adenoviruses. – 5′ C 3′
Minus strand
is copied. –
New
synthesis
leading
strand 5′ C 5′ C + 3′
Completed linear
double strand 5′ C + 3′ 3′ – C 5′
Figure 9.12

12. Covalently linked protein TP
pTP is primer
Strand displacement replication
Viral proteins

13. 9.7 DNA Tumor Viruses
Some DNA viruses can induce cancer (“tumor viruses or “oncoviruses”
Human Papilloma Viruses (HPV)
Herpesviruses

14. 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

15. 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

16. Figure 9.13b Infection + Viral DNA integrates into host DNA. Viral DNA
Tumor virus DNA +
Host DNA
Viral DNA integrates
into host DNA.
Viral DNA
Transcription of
tumor-inducing genes
Tumor virus mRNA
Transport of mRNA to
cytoplasm and translation
Figure 9.13b Polyomaviruses and tumor induction.
Viral
tumor-induction
proteins
Transformation of
cell to tumor state
Figure 9.13b

17. 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

18. 9.7 DNA Tumor Viruses Some Herpesviruses cause cancer
Epstein-Barr Virus
HHV-8
Diverse mechanisms

19. III. Viruses with RNA Genomes
9.11 Viruses That Use Reverse Transcriptase

20. 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

21. 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”

22. RNA tumor virus genome Src is an “oncogene”
C-src = normal cellular version
V-src = version carried by virus

26. 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)

27. IV. Subviral Agents
9.12 Viroids
9.13 Prions

28. 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

29. 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)

30. Figure 9.27 Figure 9.27 Prions. Neuronal cell Prnp Nucleus DNA
Transcription
Translation
Normal
function
Figure 9.27 Prions.
PrPc
(normal
prion)
PrPSc-induced
misfolding of PrPC
Abnormal
function
PrPSc
(misfolded prion)
Figure 9.27

31. Chronic Wasting Disease in deer and elk
Mad Cow Disease
Kuru, KJD in humans