The Interpretation of Evolutionary
Trees of HIV-1 env Genes as an
Indicator of Individual Immune
Response Patterns.
Chris Rhodes, Nicki Harmon
Loyola Marymount University
Department of Biology
Seaver 202 10/05/11
Outline
• Data from the Markham et al. (1998) study indicates a
possible pattern of immune response between progressor
types.
• Data from Markham et al. (1998) study was used to create
phylogenetic trees of individual subjects for 3 different
progressor types.
• Phylogenetic trees were interpreted to reveal the immune
response pattern of each subject and the possible
correlations between progressor types.
• Results indicated limited relationships between progressor
type and immune response.
Possible Immune Response
Patterns
• Markham et al. (1998) categorizes progressor types by
the rate of CD4-T cell decline.
• Different rates of CD4-T cell decline correspond to the
different patterns of immune response.
• Therefore different progressor types should also
correspond to different patterns of immune response
• Markham et al. (1998) theorized that non-progressor
types shared a similar immune response pattern.
• Does this apply to all progressor types?
Creation of Phylogenetic Trees
• Subjects were chosen based on clone sample
size.
– Rapid Progressors: Subjects 3 and 11
– Moderate Progressors: Subjects 7 and 8
– Non-Progressors: Subjects 12 and 13
• A ClustalW alignment was used to generate the
phylogenetic trees.
Outline
• Data from the Markham et al. (1998) study indicates a
possible pattern of immune response between progressor
types.
• Data from Markham et al. (1998) study was used to create
phylogenetic trees of individual subjects for 3 different
progressor types.
• Phylogenetic trees were interpreted to reveal the immune
response pattern of each subject and the possible
correlations between progressor types.
• Results indicated limited relationships between progressor
type and immune response.
Interpretations of Trees
• Trees were interpreted using standardized
criteria:
– Relative Branch Length
– Type and amount of branching
– Chronological considerations
– Clone Clustering
Types of Immune Responses
•
•
•
•
•
“Best Fit” Model
Population-specific Response
Non-selective Response
Broad Response
Adaptive Immune Response
Subject 3
Rapid Progressor
Subject 11
Rapid Progressor
Subject 7
Moderate Progressor
Subject 8
Moderate Progressor
Subject 12
Non-Progressor
Subject 13
Non-Progressor
Outline
• Data from the Markham et al. (1998) study indicates a
possible pattern of immune response between progressor
types.
• Data from Markham et al. (1998) study was used to create
phylogenetic trees of individual subjects for 3 different
progressor types.
• Phylogenetic trees were interpreted to reveal the immune
response pattern of each subject and the possible
correlations between progressor types.
• Results indicated limited relationships between progressor
type and immune response.
Immune Response Varies
between Individual Subjects
•
•
•
•
Subject 3: Adaptive Immune Response
Subject 11: Non-Selective Response
Subject 7: “Best Fit”
Subject 8: Variable (Non-Selective/
Adaptive)
• Subject 12: Broad
• Subject 13: Broad
Adjusted S Values Vary
between Individual Subjects
•
•
•
•
•
•
Subject 3: 0.216
Subject 11: 0.385
Subject 7: 0.252
Subject 8: 0.199
Subject 12: 0.191
Subject 13: 0.193
Results Indicate Limited Relationship
Between Progressor Type and Immune
Response
• Non-Progressors shared a similar broad
response pattern
• Rapid and Moderate Progressors did
not share patterns amongst their
respective types.
• Adjusted S values show no relationship
to Progressor type.
Acknowledgments
Kam D. Dahlquist, Ph.D.
Markham et al. (1998)
Lee et al. (2008)