Biomedical Engineering Reference
In-Depth Information
Fig. 9 Hepadnaviruses proteins SIR score. SIR score (Hepatitis B Virus (HBV), Ground Squirrel
Hepatitis Virus (GSHV), WoodChuck Hepatitis Virus (WHV), Duck Hepatitis B Virus (DHBV),
Goose Hepatitis B Virus) proteins. Avihepadnaviruses lack the X protein. * pvalue
<<
0
.
005
to all other hepadnaviruses in our study (GSHV, WHV, DHBV and GHBV) for the
same allele. As expected, the same pattern (namely, lower SIR score for the average
of all HBV proteins as well as specifically, Core, Surface and X proteins, and higher
SIR score for Polymerase in HBV compared with other hepadnaviruses) was shown
in most alleles, mainly in the alleles with higher frequency in human population
(T-test, p
05).
Among the proteins found to have low SIR scores in HBV, the SIR score
of Surface is relatively high while Core and X proteins have significantly lower
scores (T-test, p
<
0
.
33). This difference can originate from differences in
the immune pressure induced by these proteins or by inherent limitations on the
amino acid composition. To differentiate between the two mechanisms, we tested
the “neutral SIR” of each protein. We define the “neutral SIR” as the SIR score of
random sequences derived from scrambling each protein. In other words, instead
of scrambling full viral genomes, we scrambled each viral protein by itself 1,000
times and compared the scrambled sequences SIR score distribution to the SIR score
distribution of 107 non-scrambled sequences of the same protein (data not shown).
The real sequences of Core, Surface and X have a lower average SIR score than the
scrambled sequences (T-test, p
<
1
.
e
<
1
.
e
20). Polymerase real sequences have higher
SIR scores ( p
15) than their scrambled version. Note that the differences
between Core, X and Surface disappear when a comparison is performed between
the real SIR score and the “neutral SIR” score. Thus, Core, Surface and X seem to
induce a similar immune response.
To summarize, one can conclude from all these examples that at least two
elements affect the viral immune escape attempts:
<
1
.
e
- The timing of the protein expression.
- The level of expression.
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