1. Residue Sequence and Structure in the Re evaluation the Categorization of HIV Progression in Subjects Based on CD4 T cell Decline Rates
Angela Garibaldi & Ryan Willhite
Loyola Marymount University
BIOL
March 23, 2010

2. Outline Review of previous experiment using CD4 decline rates
Structure based hypothesis
Methods and programs used
Results
Comparison to More Recent Studies
References

3. Recap of past experiment
Evaluated the categorization of progressors based on CD4 decline rates
Analyzed two moderate progressors (6,7) with rates comparable to non-progressor 13 and rapid progressor 10.
Based on divergence and diversity subject 6 did not act as non-progressor
Subject 7 acted like a rapid progressor.

4. Hypothesis
Subject 7 will be more similar to

5. Methods Create phylogenetic trees based on amino acid sequence
Use ProtPram to analyze residue composition in subjects 6,7,5,10
Select 7 and 10 for time point analysis
First clone for selected visits used
Use Cn3d to analyze differences in 3d structure

6. Phylogenetics based on amino acid sequence
10 vs 5
10 vs 7
5 vs 7
From the subject 7 comparisons, it is clear that overall distance from 7vs5 is identical to 5vs 10, hinting that 7 is similar to 10 when compared to 5 (the control Moderate).

7. Subject 6 v 13

8. Subjects 6 v 7

9. Subjects 13 v 5

10. Subjects 6 v 5

11. Overall residue composition
All clones available were used in this analysis per individual
Rapid Progressor Subject 10 is the only one with Asn as its most prevalent residue

12. Residue composition over time

13. Residue composition over time
All clones from selected visits were used.
Subject 10, Rapid Progressor shows Asn as its prevalent residue over time.
Subject 7, Moderate Progressor begins with Asn as prevalent residue
Subject 10 showed sudden jump in Arg %. This may be an artifact.

14. Conclusions
Amino acid sequence is a secondary way to further categorize subjects into progressor groups
Subject 7, while being more phylogenetically similar, still is best fit as a moderate

15. A more recent study
Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility
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16. gp120, gp41-interactive region structure
7-stranded β-sandwich,- invariant in conformation
highly glycosylated gp120 outer domain. layers act as a shape-changing spacer, facilitating movement between outer domain and gp41-associated β-sandwich
provide for conformational diversity used in immune evasion.
A “layered” gp120 architecture allows movement among alternative glycoprotein conformations required for virus entry and immune evasion, .

17. References
Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility