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Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
Lecture 2 viral genomes, proteins, lipids dinman
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Lecture 2 viral genomes, proteins, lipids dinman

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  • 1. Lecture 2 BSCI437. VIRAL GENOMES, PROTEINS, AND LIPIDS.
  • 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. All varieties of genomes – (+) ssRNA – (-) ssRNA – dsRNA – retrovirus (+ssRNA  dsDNA) – ssDNA – dsDNA – Mixed DNA and RNA
  • 4. Thymidine tautomers Basepairs with Adenine Basepairs with Guanine 10-4 104 Tautomerization of pyramidines: the primary chemical basis for mutagenesis.
  • 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. 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. 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. 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. Cicrcular ds DNA genomes
  • 10. Linear dsDNA genomes
  • 11. Linear dsDNA genomes
  • 12. Gapped circular dsDNA genomes
  • 13. Circular ssDNA genomes
  • 14. dsRNA genomes
  • 15. (+) ssRNA genomes
  • 16. (+) ssRNA with DNA intermediate
  • 17. Linear (-) ssRNA genomes
  • 18. Segmented (-) ssRNA genomes
  • 19. Ambisense ssRNA genomes
  • 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. 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. 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. 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. 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. 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. 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. 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. 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. 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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