Table 1 Features of TSE diseases for which the RuNAway model may provide an explanation

Endogenous origin of TSE

SINEs are endogenous

TSE Agent becomes infectious

TSE causing SINE is mutated for enhanced replication

and virulence

Long latency

RT-mediated SINE gene proliferation is a slow

process. Spreading between cells is much less efficient

than viral infection

Shorter visible disease period

Transition to aggressive second RuNAway cycle

Inheritance of TSE strain

SINEs are nucleic acid and obey the laws of genetics

variation

and inheritance

Species barrier to infection

Adaptation to new RNA primer sequence required in

new host species

Absence of immune reaction

SINEs are nucleic acid and therefore not immunogenic

PrP protein required for

When overproduced, PrP protein is prone to form

pathology

aggregates which damage neighbouring cells

Agent causes PrP^Sc precipitation

SINEs can inhibit PKR a negative regulator of

translation, leading to overproduction of PrP protein

and deposition of amyloid plaques

PrP^0/0 mouse does not succumb

PrP^0/0 mouse is infected by scrapie SINEs but without

to scrapie

PrP expression no amyloid plaques can form

PrP^0/0 mouse transmits scrapie

TSE SINE replicates in PrP^0/0 mouse cells

agent

PrP^0/0 mouse transmits scrapie

TSE SINE replication is dependent on SINE RNA

agent less efficiently than

synthesis which is not stress-induced in the absence of

wildtype mouse

second RuNAway cycle