Download Interplay between Selective Pressure and Genetic Diversity of Viral

Interplay between Selective Pressure and Genetic Diversity of Viral
Populations in HIV Patients
Change in V3 nucleotide diversity
0.060
0.050
Mean sequence diversity
Hypothesis:
As the diversity of the
HIV gp120 V3 region
increased, CD4 counts
would drop.
0.040
SUBJECT 15
SUBJECT 2
0.030
0.020
V3
0.010
0.000
0
200
400
600
800
1000
CD4 count (per dcl)
Measurements of
diversity:
Compare two patients over
time: one whose CD4
counts were stable, one
whose dropped
Diversity vs. CD4 count: ClustalW was
used to produce a distance matrix using
amino acid sequence. Mean diversity
was plotted against CD4 count.
235:G
79:A
•nucleotide vs protein
alignments/trees
•Mean, maximum
•Mapping of sequence
changes onto multiple
alignment
59:C, 235:C
Rooted tree built from patient 2 V3 nucleotide
sequences
Gp120/antibody complex
Conclusions:
The hypothesis is rejected.
High levels of sequence diversity are
associated with high CD4 counts.
Potential hypothesis raised by this
observation:
There is an balance between viral
fitness and diversity. Increased
diversity can aid with immune
avoidance, however can also result
in accumulation of deleterious
mutations elsewhere in the virus
genome that decrease fitness.