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Why study evolution? Best conceptual framework for understanding origins of biodiversity Adaptations that allow organisms to exploit their environment Self discovery Keystone of biology (including human health). Lecture: HIV Motivation - PowerPoint PPT Presentation
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Why study evolution?
Best conceptual framework for understandingorigins of biodiversity
Adaptations that allow organisms to exploit their environment
Self discoveryKeystone of biology (including human health)
Lecture: HIV
I. Motivation
What can we learn when we apply evolutionary principles to our understanding of the of the HIV epidemic?? Can we use HIV to introduce us to evolutionary principles
Natural SelectionMutationGene FlowDescent with Modification
II. Prevalence & Effect
Life expectancy in Botswana
HIV is a natural selectiveagent
III. Basic Biology of HIV and Human Immunoresponse
Infectious stage
Helper T-cell
Reverse transcriptase
11. HIV replication = T-cell death
*
IV. HIV Treatment
How AZT blocks reverse transcriptase
pyrimidine
V. Evolution of HIV in Host
AZT is a selective agent On HIV
Needed to prevent replication in t-tubes
Can we predict the changes in Reverse Transcriptase* using
evolutionary principles??
*due to AZT
HIV Contributes to Collapse of Immune System in 3 Ways:
1. Continuous evolution of HIV proteins used by human immune system to recognize HIV
2. Evolution towards more and more aggressive replication
3. HIV often evolve to infect different immune cells (naïve T cells) using different immune cell receptor proteins
Years since patient became HIV Positive
Evolution at gp120 locus
Neutral evolution and progression to AIDS
Evolutionary tree for one patient Across patients progress to AIDS
HIV strains evolve to become more competitive
HIV evolves to recognize the CXCR4 receptor on Naïve helper T cells
HIV-1 interacts with a cell-surface receptor, primarily CD4, and through conformational changes becomes more closely associated with the cell through interactions with other cell-surface molecules, such as the chemokine receptors CXCR4 and CCR5.
VI. Evolution of the Host, Evidence for Genetic Variation for Resistance
Genetic variationIn Africa for Resistance to HIV
Deletion in CCR5 locus
Sex workers in Kenya having a C instead of a T at position 868 for CD4 have resistance to HIV
Two loci in human populations confer resistance to HIV
VII. Evolution of Human Specific HIVMultiple evolution of HIV
Group M HIV-1 Strains
Innocent
Guilty
Evidence
VIII. HIV is a good model to start us thinking in evolutionary terms:
1. Selective agents on host and disease
2. Source or origin of disease
3. Strategies to combat HIV
Highlights evolutionary theory:
Natural selectionMutationGene FlowDescent with Modification