Transcript Re evaluating the Categorization of HIV

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 398-01
March 23, 2010
Outline
• Review of previous experiment using CD4
decline rates
• Structure based hypothesis
• Methods and programs used
• Results
• Comparison to More Recent Studies
• References
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.
Hypothesis
• Subject 7 will be more similar to
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
Phylogenetics based on amino acid
sequence
10 vs 5
10 vs 7
5 vs 7
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
Residue composition over time
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.
3d structure of gp120
Resulting 3d structures
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
A more recent study
• Structure of HIV-1 gp120 with gp41interactive region reveals layered envelope
architecture and basis of conformational
mobility
gp120, gp41-interactive region
structure
References