Transcript Background

HIV Envelope Mutations and Onset of AIDS
C. Clower, M. Furlong and B. Haidar
Background
Fifteen HIV subjects were studied in
1998 by Richard Markham’s group. A
dataset was generated that contains
GP120 clones from the subjects over a
period of four years.
Results
Observation
Three subjects experienced an earlier
onset of AIDS (within the first 2 years of
the study) than the other subjects.
Question
Is the early onset of AIDS related to the
presence of a particular substitution
that occurs in the GP120 protein?
Example Alignment with Texshade (Biology Workbench)
Methods
A Clustal W sequence alignment of clones
from 3 separate subjects whose CD4 count
dropped below 200 after the first 18 months
was performed. Clones from the visit prior
to the CD4 drop were aligned with the
clones from the visit after the CD4 drop. A
Texshade was used to identify differences in
amino acids between the clones.
Sequences from clones prior to the CD4
drop were examined as controls. A BLAST
search was used to obtain the PDB file of
the GP120 protein. Protein Explorer was
used to visualize the crystal structure of
GP120 G chain and to identify the positions
of the amino acid substitutions that were
identified.
4
Onset of
AIDS
(visit #)
4
11
4
270-175
15
3
250-75
Subject*
CD4 Count Substitution Percent of Clones with
Decrease
Substitution (n)
470-135
RASS
NY
RK
VG
77% (13)
33 % (10)
33% (10)
100% (9)
HIV GP120 J Chain structure.
Top: Secondary Structure Shown.
Bottom: Amino acid substitutions
shaded.
* Color matches the corresponding amino acids in the structure on the immediate right.
Conclusion
The positions of all identified substitutions were on the surface of the G
chain. Each subject had a unique amino acid substitution that may have
led to the early onset of AIDS in these subjects. Future investigations
might include a study of the effect of these specific mutations on the
GP120 interactions with the CD4 T cell receptor.