Pathogens: Good Parasites Gone Bad

1. Pathogens: Good Parasites Gone Bad • At the purely intellectual level there is little to differentiate a parasite that we tolerate or a symbiotic bacterium that aids our digestion from a pathogen that makes us deathly ill. • For E. coli which normally populate our gut, there is a virulence plasmid that can transform it from a benign traveler to a serious pathogen. • Some bad pathogens start as good parasites in one species and become bad when they enter another.

2. Pathogenic vs. Parasitic Forms of E. coli

3. There is a close relationship between HIV and SIV and it has been suggested that HIV moved to humans less than 100 years ago. SIV is relatively benign in monkeys whereas HIV is lethal.

4. Pathogens Compromise Hosts in Different Ways • Bacteria commonly colonize (kill) cells, secrete toxins, or damage extracellular spaces • Viruses commonly only colonize (kill) cells since they have no life outside of cells

5. Elements of a Successful Pathogen Success as a pathogen is defined as having your DNA preserved over time. • Infectivity is important: need a good means of moving from one host to another • Proliferation: need a good mechanism to increase copies of DNA once in host • Immune or defense avoidance: most organisms have sophisticated defense mechanisms that stop pathogens and there are equally sophisticated ways parasites avoid them.

6. Virulence vs. Spread In many cases, there is an inverse relationship between the virulence of a pathogen and the spread of the pathogen Contagious Phase: inversely related to time until symptoms Virulence (Severity of disease): Directly related to response to symptoms. Example of Flu vs. Ebola Long Latency: A long latency with few symptoms can result in spread of the disease. Examples, AIDS, Herpes,

7. Immune Defenses Block Most Major Pathogens Acquired Immunity Through Vaccines Has Blocked Pathogens

8. Viral Pathogenesis at the Cellular Level Proliferation of Viruses involves several Basic Steps: • Entry to the Cell • Movement of DNA to Nucleus • Expression of Viral Proteins • Copy the viral genome • Assemble new virions • Release of active virions

9. Life Cycle of a Common Virus

10. Virus Diversity Many different viral mechanisms have developed for propagation of viral genomes. Viral shapes, sizes, genomes, methods of entry, proliferation, and release have a similar diversity. Analyses of mechanisms of viral function have provided important windows into the function of the cells that they infect.

13. Mechanisms of Viral Entry Prince of Virology. Flint et al. Fig. 5.3

14. Receptors For Viruses Can Involve Multi-protein Complexes

15. Influenza Virus Entry Princ of Virology. Flint et al. Fig. 5.7

16. Fusogenic Peptides of Several Viruses Princ of Virology. Flint et al. Fig. 5.9

17. Fusion Involves the Joining of the Outer Monolayers Then Pore Formation Princ of Virology. Flint et al. Fig. 5.10

18. Semliki Forest Virus Infection Fusion requires the low pH of the endosome Princ of Virology. Flint et al. Fig. 5.11

19. Adenovirus Directly Injects DNA into the Nucleus Princ of Virology. Flint et al. Fig. 5.12

20. Polio Virus Inserts RNA Directly into Cell Princ of Virology. Flint et al. Fig. 5.13

21. Reovirus Processing Occurs in Lysosome Princ of Virology. Flint et al. Fig. 5.14

22. HIV Infection Process Princ of Virology. Flint et al. Fig. 5.16

23. Assembly of an Active Virus

24. Vaccinia Virus Escape Mechanism

25. Herpes Virus Escape Mechanism

26. Evasion of the Immune System Occurs by Several Mechanisms Incorporation of Cellular Proteins into the viral membrane Mutation of the viral proteins can occur (reverse transcriptase has a high error frequency) In the case of parasites, they purposely change the plasma membrane proteins.

28. T-Killer Cell Can Kill Infected Cells

29. Mechanism of Recognition of Infected Cell by T-Killer

30. Readings for Next Time Alberts et al., MBOC (vol.4) Chapters 4 and 5 on chromatin structure and DNA replication plus pp 669-678 on nuclear import. Alternatively, read the equivalent chapters in one of the other Cell Biology Texts.

32. Nuclear Pore Complex Structure Princ of Virology. Flint et al. Fig. 5.19

33. Model of Nuclear Import Princ of Virology. Flint et al. Fig. 5.20

34. HIV Capsid Structure Princ of Virology. Flint et al. Fig. 5.16