1. An Introduction to the HIV Problem Space Oakwood University: Faculty Quantitative Institute Aug. 10–12, 2009

2. HIV Virus

3. 1. Virus docks with receptors on host cell (CD4 + co-receptor) 2. Reverse transcription: viral RNA  DNA 3. Viral DNA inserts into host’s DNA 4. Viral RNA transcribed & proteins assembled 5. New virions bud from host cell, killing it Life Cycle of HIV

4. The HIV Genome

5. gp 120 Structure

6. Time Course of Infection

7. The Markham et al. HIV-1 env Sequence Dataset Longitudinal study of 15 HIV+ patients from Baltimore Patients came in at 6-month intervals (“visits”) over a 4-year period Focused on the 3rd variable loop of the env gene (285 bp) At each visit, sampled ~10 viral sequences and measured CD4 levels

8. Summary of the data set Subjects: 15 Number of visits: 3-9 Number of clones per visit: 2-18 CD4 cell counts for each visit

9. Possible Investigations What is the pattern of HIV evolution within an individual? –Do the number of clones over time change in any regular way? –Do certain clones appear to survive (leave descendants) over time, while other disappear (go extinct)?

10. Possible Investigations What is the pattern of HIV evolution within the env sequence? –Are there particular positions in the sequence that are more or less likely to mutate? –Are there different rates of synonymous (silent) and non-synonymous mutations?