Viral Genetics Viruses can store their genetic information in  six different types of nucleic acid which are named based...
Viral Genetics (+/-) double-stranded DNA DNA-dependent DNA polymerase enzymes copy both  the (+) and (-) DNA strands DN...
Replication of a Double-Stranded DNA Viral Genome and                production of Viral mRNA
Viral Genetics (+) single-stranded DNA DNA-dependent DNA polymerase enzymes copy the  (+) DNA strand of the genome produ...
Replication of a Single-Stranded DNA Viral Genome and                Production of Viral mRNA
Viral Genetics (+/-) double-stranded RNA RNA-dependent RNA polymerase enzymes copy both  the (+) RNA and (-) RNA strands...
Replication of a Double-Stranded RNA Viral Genome           and Production of Viral mRNA
Viral Genetics (-) RNA RNA-dependent RNA polymerase enzymes then copy  the (+) RNA strands producing ss (-) RNA viral  g...
Replication of a Single-Stranded Minus RNA Viral     Genome and Production of Viral mRNA
Viral Genetics (+) RNA RNA-dependent RNA polymerase enzymes copy the  (+) RNA genome producing ss (-) RNA RNA-dependent...
Replication of a Single-Stranded Plus RNA Viral Genome             and Production of Viral mRNA
Viral Genetics (+) RNA Retroviruses reverse transcriptase enzymes (RNA-dependent DNA  polymerases) copy the (+) RNA geno...
Replication of a Single-Stranded Plus RNA Viral Genome   and Production of Viral mRNA by way of Reverse                   ...
Viral Genetics Viruses grow rapidly, there are usually a large  number of progeny virions per cell. There is,  therefore,...
Mutants Spontaneous mutations These arise naturally during viral replication  (Replication, Tautomeric base pairing) DN...
Mutants Types of mutation point mutants insertion/deletion mutants
Phenotypic changes seen in virus mutants Conditional lethal mutants:These mutants multiply  under some conditions but not...
Phenotypic changes seen in virus mutants Plaque size :may be larger or smaller than in the wild  type virus Drug resista...
Phenotypic changes seen in virus mutants "Hot" mutants These grow better at elevated temperatures than the  wild type vi...
Phenotypic changes seen in virus mutants Attenuated mutants Many viral mutants cause much milder symptoms (or  no sympto...
Recombination Exchange of genetic information between two  genomes "Classic" recombination :This involves breaking of  c...
Recombination Recombination of this type is very rare in RNA viruses  (No host enzymes) "copy choice" kind of mechanism ...
Recombination
Reassortment Reassortment is a non-classical kind of recombination If a virus has a segmented genome and if two  variant...
Reassortment
Applied genetics vaccine called Flumist for influenza virus The vaccine is trivalent – it contains 3 strains of  influen...
Applied genetics The vaccine technology uses reassortment to  generate reassortant viruses which have six gene  segments ...
Applied genetics
Complementation Interaction at a functional level NOT at the nucleic  acid level two mutants with a ts (temperature-sens...
Multiplicity reactivation If double stranded DNA viruses are  inactivated using ultraviolet irradiation,  we often see re...
Defective viruses Defective viruses lack the full complement of genes  necessary for a complete infectious cycle (many ar...
Defective interfering particles The replication of the helper virus may be less  effective than if the defective virus (p...
Phenotypic mixing If two different viruses infect a cell, progeny viruses  may contain coat components derived from both ...
Viral molecular genetics
Viral molecular genetics
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Viral molecular genetics

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Transcript of "Viral molecular genetics"

  1. 1. Viral Genetics Viruses can store their genetic information in six different types of nucleic acid which are named based on how that nucleic acid eventually becomes transcribed to the viral mRNA Only a (+) viral mRNA strand can be translated into viral protein
  2. 2. Viral Genetics (+/-) double-stranded DNA DNA-dependent DNA polymerase enzymes copy both the (+) and (-) DNA strands DNA-dependent RNA polymerase enzymes copy the (-) DNA strand into (+) viral mRNA Examples include most bacteriophages, Papovaviruses, Adenoviruses, and Herpesviruses
  3. 3. Replication of a Double-Stranded DNA Viral Genome and production of Viral mRNA
  4. 4. Viral Genetics (+) single-stranded DNA DNA-dependent DNA polymerase enzymes copy the (+) DNA strand of the genome producing a dsDNA intermediate DNA-dependent RNA polymerase enzymes copy the (-) DNA strand into (+) viral mRNA Phage M13 and Parvoviruses
  5. 5. Replication of a Single-Stranded DNA Viral Genome and Production of Viral mRNA
  6. 6. Viral Genetics (+/-) double-stranded RNA RNA-dependent RNA polymerase enzymes copy both the (+) RNA and (-) RNA strands of the genome producing a dsRNA genomes RNA-dependent RNA polymerase enzymes copy the (-) RNA strand into (+) viral mRNA Reoviruses
  7. 7. Replication of a Double-Stranded RNA Viral Genome and Production of Viral mRNA
  8. 8. Viral Genetics (-) RNA RNA-dependent RNA polymerase enzymes then copy the (+) RNA strands producing ss (-) RNA viral genome RNA-dependent RNA polymerase enzymes then copy the (+) RNA strands producing ss (-) RNA viral genome Orthomyxoviruses, Paramyxoviruses, Rhabdoviruses
  9. 9. Replication of a Single-Stranded Minus RNA Viral Genome and Production of Viral mRNA
  10. 10. Viral Genetics (+) RNA RNA-dependent RNA polymerase enzymes copy the (+) RNA genome producing ss (-) RNA RNA-dependent RNA polymerase enzymes then copy the (-) RNA strands producing ss (+) RNA viral genome Picornaviruses, Togaviruses, and Coronaviruses
  11. 11. Replication of a Single-Stranded Plus RNA Viral Genome and Production of Viral mRNA
  12. 12. Viral Genetics (+) RNA Retroviruses reverse transcriptase enzymes (RNA-dependent DNA polymerases) copy the (+) RNA genome producing ss (-) DNA strands DNA-dependent DNA polymerase enzymes then copy the (-) DNA strands to produce a dsDNA intermediate DNA-dependent RNA polymerase enzymes then copy the (-) DNA strands to produce ss (+) RNA genomes DNA-dependent RNA polymerase enzymes copy the (-) DNA strand into (+) viral mRNA HIV-1, HIV-2, and HTLV-1
  13. 13. Replication of a Single-Stranded Plus RNA Viral Genome and Production of Viral mRNA by way of Reverse Transcriptase
  14. 14. Viral Genetics Viruses grow rapidly, there are usually a large number of progeny virions per cell. There is, therefore, more chance of mutations occurring over a short time period Viruses undergo genetic change by several mechanisms Genetic drift: where individual bases in the DNA or RNA mutate to other bases Antigenic shift: where there is a major change in the genome of the virus. This occurs as a result of recombination
  15. 15. Mutants Spontaneous mutations These arise naturally during viral replication (Replication, Tautomeric base pairing) DNA viruses tend to more genetically stable than RNA viruses (DNA repair) Induced mutation by physical (UV light or X-rays) or chemical means (nitrous acid)
  16. 16. Mutants Types of mutation point mutants insertion/deletion mutants
  17. 17. Phenotypic changes seen in virus mutants Conditional lethal mutants:These mutants multiply under some conditions but not others A.temperature sensitive B.host range
  18. 18. Phenotypic changes seen in virus mutants Plaque size :may be larger or smaller than in the wild type virus Drug resistance: The possibility of drug resistant mutants arising must always be considered Enzyme-deficient mutants: Some viral enzymes are not always essential and so we can isolate viable enzyme-deficient mutants
  19. 19. Phenotypic changes seen in virus mutants "Hot" mutants These grow better at elevated temperatures than the wild type virus. They may be more virulent since host fever may have little effect on the mutants but may slow down the replication of wild type virions
  20. 20. Phenotypic changes seen in virus mutants Attenuated mutants Many viral mutants cause much milder symptoms (or no symptoms) compared to the parental virus - these are said to be attenuated vaccine development
  21. 21. Recombination Exchange of genetic information between two genomes "Classic" recombination :This involves breaking of covalent bonds within the nucleic acid, exchange of genetic information, and reforming of covalent bonds This kind of break/join recombination is common in DNA viruses or those RNA viruses which have a DNA phase (retroviruses). The host cell has recombination systems for DNA
  22. 22. Recombination Recombination of this type is very rare in RNA viruses (No host enzymes) "copy choice" kind of mechanism in which the polymerase switches templates while copying the RNA So far, there is no evidence for recombination in the negative stranded RNA viruses giving rise to viable viruses
  23. 23. Recombination
  24. 24. Reassortment Reassortment is a non-classical kind of recombination If a virus has a segmented genome and if two variants of that virus infect a single cell, progeny virions can result with some segments from one parent, some from the other This is an efficient process - but is limited to viruses with segmented genomes orthomyxoviruses, reoviruses, arenaviruses, bunya viruses
  25. 25. Reassortment
  26. 26. Applied genetics vaccine called Flumist for influenza virus The vaccine is trivalent – it contains 3 strains of influenza virus cold adapted strains: grow well at 25 degrees C ,grow in the upper respiratory tract temperature-sensitive and grow poorly in the warmer lower respiratory tract viruses are attenuated strains and much less pathogenic than wild-type virus
  27. 27. Applied genetics The vaccine technology uses reassortment to generate reassortant viruses which have six gene segments from the attenuated, cold-adapted virus and the HA and NA coding segments from the virus which is likely to be a problem in the up-coming influenza season
  28. 28. Applied genetics
  29. 29. Complementation Interaction at a functional level NOT at the nucleic acid level two mutants with a ts (temperature-sensitive) lesion in different genes neither can grow at a high temperature infect the same cell with both mutants, each mutant can provide the missing function of the other and therefore they can replicate
  30. 30. Multiplicity reactivation If double stranded DNA viruses are inactivated using ultraviolet irradiation, we often see reactivation if we infect cells with the inactivated virus at a very high multiplicity of infection?
  31. 31. Defective viruses Defective viruses lack the full complement of genes necessary for a complete infectious cycle (many are deletion mutants) they need another virus to provide the missing functions - this second virus is called a helper virus
  32. 32. Defective interfering particles The replication of the helper virus may be less effective than if the defective virus (particle) was not there This is because the defective particle is competing with the helper for the functions that the helper provides This phenomenon is known as interference, and defective particles which cause this phenomenon are known as "defective interfering" (DI) particles Not all defective viruses interfere, but many do
  33. 33. Phenotypic mixing If two different viruses infect a cell, progeny viruses may contain coat components derived from both parents and so they will have coat properties of both parents IT INVOLVES NO ALTERATION IN GENETIC MATERIAL We can also get the situation where a coat is entirely that of another virus

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