RNA viruses are able to evolve much more rapidly than the DNA of their eukaryotic hosts due to their lack of proofreading during replication. They undergo genetic changes through mutations, which can occur spontaneously due to errors during replication or due to environmental factors like UV light, as well as through recombination and reassortment. These genetic changes allow RNA viruses to alter their phenotypes and adapt in ways such as drug resistance, host range, temperature sensitivity, or attenuation for vaccine development.

1. VIRAL GENETICS PATHOGENESIS LIFE CYCLES VACCINE DEVELOPMENT DRUG RESISTANCE www.freelivedoctor.com

2. VIRAL GENETICS “ DNA chromosomes of eukaryotic host organisms generally require geologic time spans to evolve to the degree that their RNA viruses can achieve in a single human generation.” www.freelivedoctor.com

3. VIRAL GENETICS VIRUSES GROW RAPIDLY A SINGLE PARTICLE PRODUCES A LOT OF PROGENY DNA VIRUSES SEEM TO HAVE ACCESS TO PROOF READING, RNA VIRUSES DO NOT SEEM TO www.freelivedoctor.com

4. NATURE OF GENOMES RNA or DNA SEGMENTED OR NON-SEGMENTED www.freelivedoctor.com

5. GENETIC CHANGE MUTATION RECOMBINATION www.freelivedoctor.com

6. ORIGIN OF MUTATIONS SPONTANEOUS tautomeric form of bases polymerase errors www.freelivedoctor.com

7. Tautomeric forms of bases most of time rarely www.freelivedoctor.com

8. ORIGIN OF MUTATIONS SPONTANEOUS tautomeric form of bases polymerase errors why do some viruses seem to alter very little, even though one would expect high mutation rates? mutation rates usually higher in RNA viruses (lack of proof reading) www.freelivedoctor.com

9. www.freelivedoctor.com

10. ORIGIN OF MUTATIONS SPONTANEOUS PHYSICALLY INDUCED UV light , especially problem if no access to repair X-rays CHEMICALLY INDUCED www.freelivedoctor.com

11. TYPES OF MUTATION POINT INSERTION DELETION www.freelivedoctor.com

12. PHENOTYPES PHENOTYPE the observed properties of an organism www.freelivedoctor.com

13. PHENOTYPIC CHANGES CONDITIONAL LETHAL - multiply under some conditions but not others - wild-type (wt) grows under both sets of conditions temperature-sensitive (ts) mutants do not grow at higher temperature (altered protein) host-range mutants do not grow in all the cell types that the wt does www.freelivedoctor.com

14. PHENOTYPIC CHANGES PLAQUE SIZE may show altered pathogenicity DRUG RESISTANCE important in the development of antiviral agents ENZYME-DEFICIENT MUTANTS some genes can be ‘optional’ in certain circumstances www.freelivedoctor.com

15. PHENOTYPIC CHANGES “ HOT MUTANTS” grow better at elevated temperature than wt less susceptible to host fever response ATTENUATED MUTANTS milder (or no) symptoms vaccine development pathogenesis www.freelivedoctor.com

16. GENETIC CHANGE MUTATION RECOMBINATION www.freelivedoctor.com

17. RECOMBINATION Exchange of information between two genomes www.freelivedoctor.com

18. RECOMBINATION ‘ classic’ recombination common in DNA viruses www.freelivedoctor.com

19. COPY CHOICE RECOMBINATION +ve strand 2 +ve strand 1 www.freelivedoctor.com template switch

20. COPY CHOICE RECOMBINATION +ve strand 2 +ve strand 1 www.freelivedoctor.com -ve strand recombinant -ve strand recombinant +ve strand continues copying

21. COPY CHOICE RECOMBINATION + strand - strand + strand www.freelivedoctor.com - strand

22. COPY CHOICE RECOMBINATION + strand + strand www.freelivedoctor.com

23. Other methods recombination Take advantage quirks in virus replication eg. Coronaviruses (include SARS virus) www.freelivedoctor.com

24. RECOMBINATION - SOME USES mapping by recombination frequency mapping by marker rescue www.freelivedoctor.com

25. RECOMBINATION - SOME USES marker rescue TK mutant HSV TK - mt www.freelivedoctor.com TK - wt TK wt HSV TK - wt

26. RECOMBINATION - SOME USES mapping by recombination frequency mapping by marker rescue development of recombinant viruses for vaccines and therapeutic reasons www.freelivedoctor.com

27. RECOMBINATION - SOME USES vaccinia virus vaccinia virus for use as rabies vaccine TK rabies G rabies G T K www.freelivedoctor.com

28. raccoon eating bait with rabies vaccine in it www.freelivedoctor.com

29. REASSORTMENT www.freelivedoctor.com

30. REASSORTMENT form of recombination (non classical) very efficient segmented viruses only can occur naturally used in some new vaccines eg for influenza and rotaviruses www.freelivedoctor.com

31. cold adapted temperature-sensitive attenuated live vaccine intranasal delivery approved 2003 adapted fromTreanor JJ Infect. Med. 15:714 INFLUENZA VIRUS www.freelivedoctor.com

32. NON-SEGMENTED NEGATIVE STRAND RNA VIRUSES no classical recombination no copy choice no reassortment least ability to exchange genetic material www.freelivedoctor.com

33. other aspects of viral genetics www.freelivedoctor.com

34. COMPLEMENTATION Interaction at the functional level, NOT the nucleic acid level mutants which can complement are generally in different genes Progeny virus assembled using wt N and wt M proteins Genomes in progeny are either ts M or ts N www.freelivedoctor.com ts N wt M ts M wt N ts mutant 1 ts mutant 2

35. DEFECTIVE VIRUSES lack gene(s) necessary for a complete infectious cycle ‘ helper’ virus provides missing functions www.freelivedoctor.com package me! copy me! package me! copy me! genome

36. DEFECTIVE VIRUSES some examples of defective viruses some retroviruses (use related helper) hepatitis delta virus (uses unrelated helper) www.freelivedoctor.com

37. DEFECTIVE INTERFERING (DI) VIRUSES (PARTICLES) decrease replication of helper virus compete for viral precursors, etc. may modulate wt infections occur naturally eg. DI measles virus in subacute scelerosing panencephalitis - SSPE www.freelivedoctor.com

38. PHENOTYPIC MIXING no changes in genome possibly altered host range possibly resistant to antibody neutralization www.freelivedoctor.com

39. PHENOTYPIC MIXING PSEUDOTYPE www.freelivedoctor.com