The document discusses viral pathogenesis and genetics. It describes the cycle of viral infection as entry into host cells, primary replication at the infection site, spread within the host, and shedding/transmission. It also discusses the effects of viruses on cells and the host organism. The genetic principles of viruses are explained as mutation, selection, and recombination, which impact viral evolution, management, and experimental study.

1. Virus pathogenesis and genetics www.freelivedoctor.com

2. Viral pathogenesis Cycle of infection Entry Primary site replication Spread within the host Shedding Transmission Effects on cells Effects on organism www.freelivedoctor.com

3. Definitions Tropism what cells within the host does the virus infect? influenced by cellular receptors, intracellular molecular restricitons, route of infection & spread Prodrome early disease symptoms which are mild or non-specific Fomite an inanimate object or substance that is capable of transmitting infectious organisms from one individual to another www.freelivedoctor.com

4. Cycle of infection Secondary sites Spread Entry Shedding Shedding Local Lymphatic Neuronal Blood (viremia) Primary site www.freelivedoctor.com

5. Entry Mucous membranes or skin Respiratory Oral Sexual Ocular Percutaneous needles, wounds, bites www.freelivedoctor.com

6. Shedding, transmission Routes Respiratory Gastrointestinal (oral-fecal) Urogenital Skin Mechanisms Indirect contact Aerosols Fomites Direct contact Lesions Saliva Sex Animal or insect bites Maternal-neonatal www.freelivedoctor.com

7. Routes of entry and shedding www.freelivedoctor.com

8. Effects on cells Abortive infection Lytic infection Persistence Transformation Alteration of cellular metabolism www.freelivedoctor.com

9. Time course of infection; host response infection without spread: infection with spread: host response: www.freelivedoctor.com prodrome symptoms at secondary sites pro-drome symptoms at primary site healing innate immunity: interferon adaptive immunity: cellular, antibody inflammatory; immunopathogenesis 0 2 4 6 8 10 12 time (days)

10. Patterns of disease www.freelivedoctor.com

11. Mousepox pathogenesis www.freelivedoctor.com

12. Genetic principles Mutation Selection Recombination www.freelivedoctor.com

13. Scope of virus genetics Natural evolution of viruses Clinical management of virus infections Experimental virology www.freelivedoctor.com

14. Clinical significance of genetics Antigenic variation in HIV and influenza impact on vaccination Drug resistance in herpes and HIV Reversion of attenuation in polio vaccine Engineered vaccines temperature sensitive influenza (Flumist) www.freelivedoctor.com

15. Mutation RNA virus polymerases lack proofreading function RNA viruses mutate more frequently than DNA viruses RNA virus "quasi species" are adaptable www.freelivedoctor.com

16. Mutant phenotypes Conditional lethal Host range Temperature sensitive Drug dependence Drug resistance Plaque morphology www.freelivedoctor.com

17. Temperature sensitivity No growth Grow virus Phenotype virus www.freelivedoctor.com wt wt wt high temp low temp

18. Temperature sensitive mutants Genotype Single amino acid substitutions Mechanism Protein unstable, non-functional at an high temperature Protein stable, functional at a low temperature Isolation Random mutagenesis Brute force screening for growth at two temperatures Targeting possible Advantages Accesses any essential virus gene using a single set of protocols www.freelivedoctor.com

19. Temperature sensitivity wt 31 o C wt 40 o C ts 31 o C ts 40 o C www.freelivedoctor.com

20. Drug resistance wt -IBT wt +IBT mut -IBT mut +IBT www.freelivedoctor.com

21. Recombination and reassortment DNA viruses Breaking and joining Non-segmented RNA viruses “ copy choice” Segmented RNA viruses “ reassortment” Impact Intrinsically interesting Virus evolution Laboratory virology www.freelivedoctor.com

22. DNA virus recombination www.freelivedoctor.com

23. RNA virus recombination Copy choice www.freelivedoctor.com

24. RNA virus reassortment www.freelivedoctor.com

25. Summary: Pathogenesis & Genetics Effects on cells Abortive, lytic, persistent, latent, transforming infections Cycle of infection Effects on the organism Genetics Mutation, genotype, phenotype, reversion, recombination www.freelivedoctor.com

26. For each virus, know: Structure Pathogenesis transmission/entry/shedding replication spread immune response/counter response damage/disease mechanism Diagnosis Treatment/prevention drugs vaccines www.freelivedoctor.com