Transcript HIVstructureNickiSamFINAL

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 nonprogressor types, divergence between sequences should
be low.
• We expect changes in sequence between the nonprogressors 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)