Evolutionary Principles in Viral Epitopes - Mathematical Methods and Models in Biomedicine - page 60

numbers shows that within the broad specificity of human MHC to preferentially
bind epitopes with viral amino acid distribution, viruses specifically mutate their
epitopes to limit detection.

3.2 Human and Non-human Hosts

Among viruses, the attempts to mutate epitopes on human HLA alleles should only
be observed in human viruses (viruses infecting a human host). We compared the
epitope density in viruses infecting a human host and the epitope density in their
nonhuman counterparts. In order to compare viruses from human and non human
hosts, we used three groups of viruses from different families. We compared the
SIR scores of human herpesviruses and the ones of non-human herpesviruses. Five
human and 18 non-human herpes strains were tested on human MHC alleles [ 55 ]
(Fig. 3 a). The average SIR score of the human herpesviruses was lower than their
non-human counterparts (T-test, p 003). A similar result can be observed when

comparing HIV I and II with the respective simian immunodeficiency virus (SIV)
from which they originated [ 56 ]( p

< 0 .

02). We computed the SIR score of all
HIV-1, HIV-2, SIVcpz, SIVsm, and SIVmac sequences in the LANL and NCBI
databases [ 30 ]. The SIVcpz, which is the ancestor of HIV-1, has a higher SIR
score than average SIR score of all HIV-1 sequences. The SIR score of HIV-2 is
also smaller than the SIR scores of its ancestors SIVsm and SIVmac [ 56 ](Fig. 3 b).
Another virus with human strains as well as homologues infecting other species is
Hepatitis B virus (HBV). Viruses similar to HBV exist, among others, in ducks and
squirrels. As was the case for the herpes and the HIV, the SIR score of non-human
hepatitis viruses is approximately 1, while the SIR score of the HBV is, lower than
1(Fig. 3 c) (T-test, p

< 0 .

01).
More generally, when comparing the SIR scores of all human-infecting viruses,
it is significantly lower than the one of non-human viruses (Fig. 3 d) (T-test, p

< 0 .

<

1 7). However, this last result should be taken with a grain of salt, since the

SIR score of different virus families can significantly vary. Thus, the average over
multiple families is affected by the number of available fully sequenced viruses
in each family. The human papillomavirus (HPV) family (papillomaviridae) is one
of the most highly sequenced human viral families. HPV have a low SIR score,
reducing the average human viruses SIR score. Thus, the proper analysis is the case-
by-case comparison of similar viruses, as was done in the herpes, HIV and HBV
cases. In the following sections, we discuss each such virus separately.

. e −

3.3 Herpes: The Effect of Different Viral Life Stages

The herpesviridae is a large family of double-stranded DNA viruses that infect
a wide range of hosts. Based on biological characteristics the herpesviruses are