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LMU Department of Biology 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. 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.

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

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

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.

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.

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

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.

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.

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

Analysis of Multiple Sequences Alignment Shows Conservation of Residues

Secondary Structure Is Maintained Throughout The Subjects

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.

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.

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.

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)