TO WHAT EXTENT IS STRAIN VARIATION EVIDENCE FOR AN INDEPENDENT GENOMEIN THE AGENT OF THE TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

The apparent existence of multiple strains of the 'transmissible agent ' associated with spongiform encephalopathy (prion disease) has been u sed to support the argument that these diseases are caused by an indep endent, replicating agent with its own genome. However, the length of the incubation period (time from injection of infected material to ons et of clinical signs) and the lesion profile (regional distribution of neuropathology), which are the key features used to define the strain of agent, have been shown to be influenced by the prion protein of th e host and the donor, such that it is only the variance in these measu res which remains after variation due to all other factors has been ta ken into account, which can be used as evidence for the existence of d ifferent strains of agent. The donor is the animal from which infectio us material is prepared for injection into the host. Almost all aspect s of pathogenesis, including most of the variance in incubation time, can be explained in terms of interactions between donor and host prion protein. We argue that the number of separate strains of agent may be more limited than is usually represented. It is important to distingu ish between the hypothesis that the prion protein of the host 'permits ' the selection of mutated strains and the hypothesis that it 'induces ' changes in the agent. The former is consistent with the concept of a n agent with an independent genome while the latter is consistent with the concept that 'strain of agent' is another expression of the invol vement of prion protein in the pathogenesis of transmissible spongifor m encephalopathy. (C) 1996 Academic Press Limited