Download Population Dynamics and HIV

Animal Viruses
– Viruses that infect
animals are
common causes
of disease.
– From Medical
Virology 4th Ed.
By White and
Fenner
Other resources
• http://www.cdc.gov/
• http://aids.gov/hiv-aids-basics/hiv-aids101/what-is-hiv-aids/index.html
HIV/AIDS
HIV, the AIDS Virus
– HIV is a
retrovirus.
• A retrovirus is
an RNA virus
that
reproduces by
means of a
DNA
molecule.
• It copies its
RNA to DNA
using reverse
transcriptase
– How HIV reproduces inside a CD4 + T lymphocyte
(T cell)
Integrase
Protease
Glycoproteins
gp120, gp41
– AIDS is
• Acquired immune deficiency syndrome.
• The disease caused by HIV infection.
• Treated with many classes of drugs:
–
–
–
–
Reverse transcriptase inhibitors (AZT, ddC,…)
Protease inhibitors
Integrase inhibitors
Fusion inhibitors
http://www.youtube.com/
watch?v=RO8MP3wMv
qg
Population Dynamics
• How does a population of HIV viruses in a
human body change over time?
What is a Population?
“A group of interacting individuals
belonging to one species in the
same geographic area at the
same time.”
Population of viruses
in a single person
at the same time
Population of humans
in the same area
at the same time
Population Dynamics
• How does a population of HIV viruses in a
human body change over time?
HIV Disease progression
HIV drug resistance:
How does this happen?
2537 patients with HIV in the UK
from 1996-2003.
None had received antiretrovirals before they joined the
study.
They were then placed on
combination anti-retroviral
therapy.
HIV drug resistance
Initial ideas
• What might be the characteristics of a
population of HIV viruses at each of the
following time points:
• Time 0 – before anti-HIV drug is taken
• Time 1 – when the anti-HIV drug is started
• Time 2 – 7 years later while the anti-HIV
drug is still being taken.
The Darwinian View of Life
The
evolutionary
view of life
came into
focus in
1859 when
Charles
Darwin
published
The Origin
of Species.
– Darwin’s book developed two main points:
• Descent with modification
• Natural selection
EVOLUTION
The Mechanism of
EVOLUTION
Natural Selection
– Darwin was struck by the diversity
of animals on the Galápagos Islands.
– He thought of adaptation to the environment and
the origin of new species as closely related
processes.
•As populations separated by a geographic barrier
adapted to local environments, they became separate
species.
–Fourteen species of Galápagos finches have beak
shapes adapted to suit their environments.
Darwin’s Inescapable
Conclusion
– Fact 1: Potential for overproduction and
competition for existence
– Fact 2: Individual variation
– The inescapable conclusion:
Unequal reproductive success
• Darwin called this process natural selection.
• The result of natural selection is adaptation.
Observing Artificial Selection
Artificial selection is the selective breeding
of domesticated plants and animals by
humans.
Observing Natural Selection
– There are many examples of natural selection
in action.
• The development of antibiotic-resistant bacteria is
one.
Tuberculosis
- MDR-TB
- XDR-TB
Staphylcoccus aureus (staph)
- CA-MRSA
Darwin’s Inescapable
Conclusion
– Fact 1: Potential for overproduction
and competition for existence
Evidence
for HIV?
– Fact 2: Individual variation
– The inescapable conclusion:
Unequal reproductive success
• Darwin called this process natural selection.
• The result of natural selection is evolution when a population
has adapted to its environment.
How do we study
overproduction and struggle
for existence?
Look to Ecology
– Ecology
• Is the scientific study of the interactions
between organisms and their environments.
A Hierarchy of Interactions
Population Growth Models
– Two models, the exponential growth model
and the logistic growth model, will help us
understand population growth.
– The growth rate
• Is the change in population size over time
The Exponential Growth Model:
The Ideal of an Unlimited
Environment
– The exponential growth model
• Describes the rate of expansion of a population
under ideal, unregulated conditions.
– Enough food and resources
– Waste is washed or taken away or not significant
Copyright © 2007 Pearson Education Inc., publishing as Pearson Benjamin Cummings
Figure 18.17
The Logistic Growth Model: The
Reality of a Limited Environment
– In nature, a population may grow
exponentially for a while, but eventually
one or more environmental factors will limit
its growth.
– Population-limiting factors restrict
population growth.
Copyright © 2007 Pearson Education Inc., publishing as Pearson Benjamin Cummings
– A comparison of the logistic growth model
and the exponential growth model
–Carrying capacity
•Is the number of individuals in a population that the
environment can just maintain with no net increase
or decrease.
HIV Disease progression:
Modified Logistic Growth Model
HIV can reproduce over a billion times a day.
It is in a constant struggle for existence
with the immune system and anti-HIV drugs.
HIV drug resistance:
How does this happen?
2537 patients with HIV in the UK
from 1996-2003.
None had received antiretrovirals before they joined the
study.
They were then placed on
combination anti-retroviral
therapy.
Darwin’s Inescapable
Conclusion
– Fact 1: Potential for overproduction and
competition for existence
– Fact 2: Individual variation
Evidence
for HIV?
– The inescapable conclusion:
Unequal reproductive success
• Darwin called this process natural selection.
• The result of natural selection is evolution when a
population has adapted to its environment.
Random Mutations in the
genome are the basis of
individual variation
• Base substitution
– Silent mutation
– Missense mutation
– Nonsense mutation
• Insertion or deletion
– Reading frame shift
• They occur at random by
– Errors in DNA replication by enzymes
– Exposure to mutagens (UV, chemicals, etc…)
• Mutations can be beneficial, harmless, or harmful
How does the
anti-HIV drug
AZT work?
Figure 10.1
How do mutations in the
genome cause resistance?
How do mutations in the
genome cause resistance?
How do mutations in the
genome cause resistance?
• http://www.nature.com/nrg/journal/v9/n2/fig_t
ab/nrg2273_F2.html
• Take a look at the movie showing HIV drug
action again. Your job: add in a mutation
that changes the structure of the enzymes,
that allows the enzymes to function even in
the presence of the drug.
• http://www.youtube.com/watch?v=RO8MP3wMvqg
Natural Selection at work
Time 0:
Overproduction and
pre-existing individual variation
caused by random mutations
Time 1:
Struggle for existence:
Environmental
Selection
Time 2:
Population
has evolved
HIV drug resistance! How??
1.
Overproduction
Large amount of offspring
•
2.
Heritable
Individual
variation
Reverse transcriptase (RT) is error-prone!
•
3.
Struggle for 4.
existence
5.
HIV replicates over a billion times a day
About 50% of HIV DNA transcripts made by RT
contain at least one mistake (mutation) at random.
Random mutation is heritable
Mutants are better able to reproduce in
selective environment
Population adapts to change in environment,
resulting in a different population = evolution
Microbe evolution TODAY
Video 1: HIV Evolution on PBS (7:30 min)
Video 2: MDR-TB Evolution on PBS (9 min)
http://www.youtube.com/watch?v=
34GeUa7RzvY
http://www.youtube.com/watch?v=
W-WumllRPLI&feature=related
• Other slides for questions….
– The reproductive cycle of an enveloped virus
Influenza virus
Simplified Viral Reproductive Cycle
An Example of
Mutations that have an
effect on drug response
in humans.
– In 2003, the Food and Drug
Administration
• Approved the drug gefinitib for the
treatment of lung cancer.
• Gefinitib blocks signaling from a
growth factor receptor (a receptor
that signals the cell to grow and
divide!) found in abundance on
some lung cancer cells.
– Unfortunately, gefinitib is
ineffective for many patients.
Copyright © 2007 Pearson Education Inc., publishing as Pearson Benjamin Cummings
– A 2004 study found that genetic differences
among patients affected their response to
the drug,
• Pre-existing individual variation
in a population of
humans affects their
ability to respond to
the drug.
How do mutations cause drug
resistance?
• http://www.cabm.rutgers.edu/~kalyan/RT_imgs/index.html
– Dr. Kalyan Das at Rutgers University