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An Introduction to the HIV Problem Space

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

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An Introduction to the HIV Problem Space

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

  2. HIV Virus

  3. Life Cycle of HIV 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

  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?

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