Identifying transmission of a TSE from one species to
another (or from animal to animal within a species) depends on the availability
of a test that can distinguish the different strains of TSE.
- to date no in vitro test is capable of
distinguishing the various strains of TSE
- i.e. differentially recognizes the tertiary structure
of PrPs
- only the tedious TSE
serial passage test has the ability to distinguish the various strains
- as shown in the figure below passaging a TSE into
similar but different strains of the same species may result in the diagnosis
of different strains when examining the recipient (i.e. the hampsters differ
in the development of a TSE)
- clinical variables (time to onset, pathology,
species barrier) depends on:
- the strain of TSE used for infection (often
what is trying to be determined)
- the species of the donor
- the genotype of the donor
- the species of the recipient
- genotype of the recipient
- number of serial passages within the same
species
- the time to onset of the disease is ofter
longer after TSE infection from one species to another and shortens
with subsequent passaging within the recipient species
- degree of lesion development or even the
presence or absence of PrP resistant to proteinase K will change
with serial passaging within the same recipient species
- however upon passaging into isogenic animals of
the same species (mice in the figure below) or back into the original donor
species, it can be shown that the characteristics of the TSE strain have been
maintained (fidelity of passage)
- fidelity of transfer is of considerable concern
- early evidence from serial passaging of TSEs through
different species or non-isogenic animals within a species lead to the conclusion
that new strains could develop with passaging (see figure below)
- in the example below, passaging through different
strains of hamsters altered the TSE such that subsequent passaging into
the same strain of mouse or back into cattle resulted in a new form of
TSE
- although two intermediate speces are shown in
the figure below, one may be sufficient to cause the effect
- the current evidence indicates that TSE fidelity
is maintained although development of new strains is possible
- the genotype
of the infected animal may alter the phenotype of the disease and presumably
the exact folding of PrPSc
- it is possible that an alteration in folding is
maintained resulting in a new TSE strain when subsequently passaged
Keep in mind that fidelity of transfer is not the same
as alterations in the
species barrier, when the species barrier is bypassed the strain of TSE
is maintained; loss of fidelity means a new strain of TSE arises independent
of changes in the species barrier