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Changes In Protein Sequences Of the HIV-1 gp120 V3 Region In Non-Progressor Types

Changes In Protein Sequences Of the HIV-1 gp120 V3 Region In Non-Progressor Types. Nicki S.Harmon Samantha M. Hurndon LMU Department of Biology BIOL 368 11/2/11. Outline. The V3 region and non-progressor types as defined by Markham.

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Changes In Protein Sequences Of the HIV-1 gp120 V3 Region In Non-Progressor Types

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  1. Changes In Protein Sequences Of the HIV-1 gp120 V3 Region In Non-Progressor Types NickiS.Harmon Samantha M. Hurndon LMU Department of Biology BIOL 368 11/2/11

  2. Outline • The V3 region and non-progressor types as defined by Markham. • Changes in Amino Acid Sequence between various subjects in the moderate progressor and non-progressor categories. • Sequence Alignment tools and Secondary Structure tools were used to identify changes between the subjects. • What the data reveals about the relation between sequence and secondary structure in the V3 region of HIV-1.

  3. The Amino Acid Sequence of the V3 Region Plays A Significant Role in CD4 Binding. • The V3 region of the gp 120 env protein is a variable loop with a high mutation rate. • V3 is what binds to the CD4 receptor sites on cell. • The amino acid sequence determines how the V3 region will function. • And therefore, how the CD4 will interact

  4. HIV-1 Progresses at Different Rate • Markham observed 3 types of progressors • Non-progressors • Maintained CD4 T cell levels above 650 throughout the Observation period. • Moderate • CD4 T cell levels declined to 200-650 during the observation period • Rapid • Having attained a level of fewer than 200 CD4 T cells

  5. Outline • The V3 region and non-progressor types as defined by Markham. • Changes in Amino Acid Sequence between various subjects in the moderate progressor and non-progressor categories. • Sequence Alignment tools and Secondary Structure tools were used to identify changes between the subjects. • What the data reveals about the relation between sequence and secondary structure in the V3 region of HIV-1.

  6. The Non-Progressor Types Should Have Amino Acid Sequences that are Closely Related • Since the CD4 T cells are being maintained in the non-progressor types, divergence between sequences should be low. • We expect changes in sequence between the non-progressors to not be significant. • There should be points of divergence between a moderate progressor and the non-progressors.

  7. Methods were Based off Markham’s Findings • The subjects that we selected for our study were subjects 2, 12, 13 and 8. • Subject 2, 12 and 13 are non progressor types • Subject 8 is a moderate progressor that will be used as a comparison to our non progressor subjects

  8. Outline • The V3 region and non-progressor types as defined by Markham. • Changes in Amino Acid Sequence between various subjects in the moderate progressor and non-progressor categories. • Sequence Alignment tools and Secondary Structure tools were used to identify changes between the subjects. • What the data reveals about the relation between sequence and secondary structure in the V3 region of HIV-1.

  9. Determination of Sequences were Randomly Selected • Due to the nature of the non-progressor type, sequence selection can be random. • Subject 8 showed a change over the course of the study. • Due to this change sequences from the first and last visits were chosen.

  10. Amino Acid Sequences were Retrieved For Our Subjects • The program Bedrock was use to access our sequences.

  11. Analysis of Multiple Sequences Alignment Shows Conservation of Residues

  12. Secondary Structure Is Maintained Throughout The Subjects

  13. Outline • The V3 region and non-progressor types as defined by Markham. • Changes in Amino Acid Sequence between various subjects in the moderate progressor and non-progressor categories. • Sequence Alignment tools and Secondary Structure tools were used to identify changes between the subjects. • What the data reveals about the relation between sequence and secondary structure in the V3 region of HIV-1.

  14. Conclusions We Can Make Based Off Sequences From Subjects 2, 12, 13 & 8 • The Non-Progressor types had similar amino acid sequences. • There were changes between the non-progressors and subject 8 that could account for subject 8 being a moderate progressor. • Secondary structure was not affected by these changes in sequence.

  15. Positive In Vivo Selection of the HIV-1 Envelope Protein gp120 Occurs at Surface-Exposed Regions -Rapid Evolution of HIV represents a major challenge to drug vaccines -Looked at HIV-1 infected persons who interrupted antiretroviral therapy -Conducted a long-term survey of sequence evolution in 20 HIV-1- Infected persons. Collected from clonal sequences of C2-V3-C3 regions. -Found that positively selected amino acid changes occurred predominantly at exposed locations on the virions surface.

  16. References • 21 Markham et al. (1998), Cohen et al. (2008) review, Exploring HIV Evolution Handout • Kwong et al. (1998), Stanfield et al. (1999), Stanfield et al. (2003) • Positive In Vivo Selection of the HIV-1 Envelope Protein gp 120 Occurs at Surface-Exposed Regions, B. Joobs, et al. (2007)

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