Transcript lecture 2

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.
Pathogenic vs. Parasitic Forms
of E. coli
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.
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
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.
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,
Immune Defenses Block Most
Major Pathogens
Acquired Immunity Through Vaccines Has Blocked Pathogens
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
Life Cycle of a
Common Virus
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.
Mechanisms of Viral Entry
Prince of Virology. Flint et al. Fig. 5.3
Receptors For Viruses Can Involve
Multi-protein Complexes
Influenza Virus Entry
Princ of Virology. Flint et al. Fig. 5.7
Fusogenic
Peptides of
Several Viruses
Princ of Virology. Flint et al.
Fig. 5.9
Fusion
Involves the
Joining of the
Outer
Monolayers
Then Pore
Formation
Princ of Virology. Flint
et al. Fig. 5.10
Semliki Forest
Virus Infection
Fusion requires the low pH of the
endosome
Princ of Virology. Flint et al. Fig. 5.11
Adenovirus Directly
Injects DNA into the
Nucleus
Princ of Virology. Flint et al. Fig. 5.12
Polio Virus Inserts
RNA Directly into
Cell
Princ of Virology. Flint et al.
Fig. 5.13
Reovirus Processing
Occurs in Lysosome
Princ of Virology. Flint et al. Fig. 5.14
HIV Infection
Process
Princ of Virology. Flint et al.
Fig. 5.16
Assembly of an Active Virus
Vaccinia Virus Escape Mechanism
Herpes Virus Escape Mechanism
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.
T-Killer Cell Can Kill
Infected Cells
Mechanism of Recognition of
Infected Cell by T-Killer
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.
Nuclear Pore Complex Structure
Princ of Virology. Flint et al.
Fig. 5.19
Model of Nuclear Import
Princ of Virology. Flint et al. Fig. 5.20
HIV Capsid Structure
Princ of Virology. Flint et al.
Fig. 5.16