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

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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

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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.

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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

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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

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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.

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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.

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Methods were Based off Markhams 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

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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.

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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.

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Amino Acid Sequences were Retrieved For Our
Subjects

• The program Bedrock was use to access our
  sequences.

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Analysis of Multiple Sequences Alignment Shows
Conservation of Residues
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Secondary Structure Is Maintained Throughout The
Subjects
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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.

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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.

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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.
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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)