Evolutionary Principles in Viral Epitopes - Mathematical Methods and Models in Biomedicine - page 66

2.5

2

1.5

1

0.5

0

Fig. 7 The SIR score of all candidate HLA alleles for different proteins in serotyped hosts.
Tat and Rev systematically have low SIR scores, while Gag has high ones. Not all proteins had
measured sequences in all alleles. Empty spots represent protein/allele combinations with less than
ten sequences

A very different trend was observed in Gag/Pol. Gag has originally a large number
of computed epitopes, including the immunodominant SLYNTIATL. The original
epitopes are actually highly conserved over time, and a good alignment to the
original epitopes can be found in 85 % of the sequences in the last recorded
period. Pol demonstrates a similar epitope evolution to Gag, showing again the very
different evolution of Tat, Rev, Gag and Pol.

3.5 Early Versus Late Viral Proteins in Multiple Viruses

The main conclusion from these two examples is that early proteins are selected to
present less epitopes than late ones. We have systematically tested if that was the
case in the vast majority of viruses [ 57 ]. We have compared early to late proteins
in 24 different viruses, mostly adenoviruses, herpesviruses and HPV. In most HLA
alleles tested the average SIR score ratio of late to early proteins is higher than one.
This result is valid for most viruses, as well as for the average of all viruses (all
positive values in Fig. 8 represent allele/virus combination with a higher epitope
density in late proteins than in early proteins). The difference between early and
late proteins is significant, when comparing the average SIR over all alleles (T test,
p

< 0 . 0001), or when the SIR for each allele is taken into account (Anova, p <

1 . e − 100).