Lecture 2 BSCI437. VIRAL
GENOMES, PROTEINS, AND
LIPIDS.
Criteria for viral genomes
• Must use same genetic code as
host
• Must use same biomolecules as
host: Nucleic Acids. Prote...
All varieties of
genomes
– (+) ssRNA
– (-) ssRNA
– dsRNA
– retrovirus (+ssRNA  dsDNA)
– ssDNA
– dsDNA
– Mixed DNA and RNA
Thymidine tautomers
Basepairs
with
Adenine
Basepairs
with
Guanine
10-4
104
Tautomerization of pyramidines:
the primary che...
Tautomerization of pyramidines:
Cytosine tautomerization is an order of
magnitude less.
Basepairs
with
Guanine
Basepairs
w...
Properties of viruses
relative to genome type
• Size Range: Range from encoding
as little ≈2 kb (Circoviruses), to
as larg...
Genome topologies
Includes every possible
combination of:
• double stranded or single
stranded,
• linear or circular,
• co...
Structure & Composition of
Genomes: Generally, any and all
possible combinations are known.
Composition. Can be RNA,
DNA, ...
Cicrcular ds DNA
genomes
Linear dsDNA genomes
Linear dsDNA genomes
Gapped circular dsDNA
genomes
Circular ssDNA genomes
dsRNA genomes
(+) ssRNA genomes
(+) ssRNA with DNA
intermediate
Linear (-) ssRNA genomes
Segmented (-) ssRNA genomes
Ambisense ssRNA genomes
Special properties
• Terminal Redundancy:
genomes of many viruses are
terminally redundant. Used
as tools for replication,...
Special properties
• Covalent Modifications:
Includes modifications to
nucleic acids (eg.
methylation,
pseudouridylation, ...
Genome condensation
strategies
• Hijack host proteins for some or
all replication functions
• Overlapping genes
• Genes on...
Viral adaptation and
evolution through mutation
• Three major phenomena are
used:
1. Base misincorporations by
polymerases...
Mutation
• Viruses are subject to the same type
of mutations as other organisms:
– Transitions and transversions
– Deletio...
Genome related
phenomena
• Reassortment: exchange of
genome segments in
segmented viruses. e.g.
Influenza
• Transduction: ...
Non-Genome related
phenomena
• Interference: inhibition of
replication or infection of
one type of virus by another.
e.g. ...
Viral Proteins
As few as 2 and as many as >50 virus-
encoded proteins. Generally divided into
“Structural” and “Non-struct...
Viral Lipids
• Viral envelopes contain
complex mixtures of neutral
lipids, phospholipids and
glycolipids.
• As a rule, the...
Host-encoded
molecules
• Viruses can pick up molecules
from host cells.
• Lipids.
– Make up bulk of viral envelopes.
– Tak...
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Lecture 2 viral genomes, proteins, lipids dinman

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Lecture 2 viral genomes, proteins, lipids dinman

  1. 1. Lecture 2 BSCI437. VIRAL GENOMES, PROTEINS, AND LIPIDS.
  2. 2. Criteria for viral genomes • Must use same genetic code as host • Must use same biomolecules as host: Nucleic Acids. Proteins, carbohydrates and lipids. • Modifications (polyadenylation of mRNA, capping, splicing) must either depend on viral enzymes or host enzymes • Continuous pressure to minimize size • Fast replication (especially important in bacteria where virus must keep up with host) • Genome packaging. – It takes a capsid of several million Daltons to package a 10 kb genome. – The larger the genome the larger the capsid must be and this means more energy and time required for synthesis).
  3. 3. All varieties of genomes – (+) ssRNA – (-) ssRNA – dsRNA – retrovirus (+ssRNA  dsDNA) – ssDNA – dsDNA – Mixed DNA and RNA
  4. 4. Thymidine tautomers Basepairs with Adenine Basepairs with Guanine 10-4 104 Tautomerization of pyramidines: the primary chemical basis for mutagenesis.
  5. 5. Tautomerization of pyramidines: Cytosine tautomerization is an order of magnitude less. Basepairs with Guanine Basepairs with Adenine 10-5 105 H Enamine Enimine Cytosine tautomers
  6. 6. Properties of viruses relative to genome type • Size Range: Range from encoding as little ≈2 kb (Circoviruses), to as large as 800 kb (Mimiviruses) • Variations (single molecule or segmented) • NTP Polymerases: Viral or host origin • Fidelity of replication – From high fidelity (<10-9 /nt) to low fidelity (10-4 /nt) • Recombination • Reassortment
  7. 7. Genome topologies Includes every possible combination of: • double stranded or single stranded, • linear or circular, • contiguous, segmented, or gapped • polarity: Single stranded (+) strand, (-) strand, or ambisense
  8. 8. Structure & Composition of Genomes: Generally, any and all possible combinations are known. Composition. Can be RNA, DNA, and/or any combination thereof! •DNA or RNA •DNA with short RNA segments •DNA or RNA with covalently attached protein (e.g. polio)
  9. 9. Cicrcular ds DNA genomes
  10. 10. Linear dsDNA genomes
  11. 11. Linear dsDNA genomes
  12. 12. Gapped circular dsDNA genomes
  13. 13. Circular ssDNA genomes
  14. 14. dsRNA genomes
  15. 15. (+) ssRNA genomes
  16. 16. (+) ssRNA with DNA intermediate
  17. 17. Linear (-) ssRNA genomes
  18. 18. Segmented (-) ssRNA genomes
  19. 19. Ambisense ssRNA genomes
  20. 20. Special properties • Terminal Redundancy: genomes of many viruses are terminally redundant. Used as tools for replication, expression, integration into host chromosomes, and for protection of ends. Examples include λ, retro-, adeno-, parvo-, pox-, bunya-, and arenaviruses.
  21. 21. Special properties • Covalent Modifications: Includes modifications to nucleic acids (eg. methylation, pseudouridylation, etc.), and covalent linkage with proteins. Of the latter, proteins covalently linked to the 5' ends of picorna- and adenoviruse RNAs play important roles in cap- independent translation.
  22. 22. Genome condensation strategies • Hijack host proteins for some or all replication functions • Overlapping genes • Genes on both strands of dsDNA in opposite directions • Multiple splicing of the same transcript to make many different proteins (only need 1 promoter) • Polyprotein production from one mRNA and subsequent proteolytic cleavage • Frameshift mechanisms allow downstream out of frame genes to be made at appropriate proportions
  23. 23. Viral adaptation and evolution through mutation • Three major phenomena are used: 1. Base misincorporations by polymerases. 2. Recombination by breakage and religation in all DNA viruses or RNA viruses with a DNA intermediate or by Copy- choice with many ssRNA viruses. 3. Reassortment in the case of viruses with multipartite genomes (more than one segment)
  24. 24. Mutation • Viruses are subject to the same type of mutations as other organisms: – Transitions and transversions – Deletions – Insertions – Nonsense mutations. • Mutations can be spontaneous or induced. – Inducing agents commonly used to directly mutate the virus for study. – Mutations can be used to map genes in viruses just as they are used to map in bacteria. • Mutations are also useful in determining the function of a protein. – Conditional mutants- a mutant phenotype that is replication competent under “permissive” but not “restrictive” or “nonpermissive” conditions. • Mutations are subject to reversion either at the same or a different (pseudorevertant) location in the genome. • Mutants can also be complemented by other viral strains in a superinfection.
  25. 25. Genome related phenomena • Reassortment: exchange of genome segments in segmented viruses. e.g. Influenza • Transduction: Incorporation of host cellular genes into viral genome, e.g. RSV • Attenuation: virulence lost but virus can still replicate in host. • Recombination: Exchange of genetic information between two or more virus genomes.
  26. 26. Non-Genome related phenomena • Interference: inhibition of replication or infection of one type of virus by another. e.g. HIV-1 prevention of CD4 expression in infected cell; Defective Interfering Particles in plant viruses. • Phenotypic mixing: exchange of envelopes or coat proteins between different viruses. “Pseudotypes”
  27. 27. Viral Proteins As few as 2 and as many as >50 virus- encoded proteins. Generally divided into “Structural” and “Non-structural”. • Structural: These compose the capsids/nucleocapsids, and envelope proteins. – Primary function of those involved in capsid/nucleocapsids is to serve as building blocks for the virion (viral particle). • Envelope proteins are typically glycoproteins in the form of spikes or projections. – Typically, these serve as receptors for host cell-surface glycoproteins and are involved in viral attachment and entry into cells (infection). • Non-structural: proteins with enzymatic, virus replicative, or for interactions with host-cell encoded factors. – Examples from HIV include Pol, Int, RNase H, Integrase, Nef, Vif, and Tat.
  28. 28. Viral Lipids • Viral envelopes contain complex mixtures of neutral lipids, phospholipids and glycolipids. • As a rule, their composition resembles that of the host cell membrane from which the envelope was derived.
  29. 29. Host-encoded molecules • Viruses can pick up molecules from host cells. • Lipids. – Make up bulk of viral envelopes. – Taken from host cellular membranes. • RNAs. – tRNAs used for priming. – 5S rRNA and other trans- acting factors used in translation initiation.

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