An Introduction to the HIV Problem Space

Oakwood University:Faculty Quantitative Institute

Aug. 10–12, 2009

HIV Virus

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

The HIV Genome

gp 120 Structure

Time Course of Infection

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 loopof the env gene (285 bp)

• At each visit, sampled ~10 viral sequences and measured CD4 levels

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

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)?

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?