The Interpretation of Evolutionary Trees of HIV-1 env Genes as an Indicator of Individual Immune Response Patterns.

1
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

2
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.

3
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?

4
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.

5
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.

6
Interpretations of Trees

• Trees were interpreted using standardized
  criteria
• Relative Branch Length
• Type and amount of branching
• Chronological considerations
• Clone Clustering

7
Types of Immune Responses

• Best Fit Model
• Population-specific Response
• Non-selective Response
• Broad Response
• Adaptive Immune Response

8

• Subject 3
• Rapid Progressor

9

• Subject 11
• Rapid Progressor

10

• Subject 7
• Moderate Progressor

11

• Subject 8
• Moderate Progressor

12

• Subject 12
• Non-Progressor

13

• Subject 13
• Non-Progressor

14
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.

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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

16
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

17
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.

18
Acknowledgments

• Kam D. Dahlquist, Ph.D.
• Markham et al. (1998)
• Lee et al. (2008)