Does transmissibility necessarily imply infectivity in spongiform encephalopathy?

Abstract

The essential biologic properties inherently acquired subsequent to conformational transformation of the α-helical molecular structure of the normal cellular PrPc isoform to the β-sheet molecular tertiary structure of the abnormal PrPsc associated with a rapidly spreading form of neuronal cell death of spongiform encephalopathy are unknown. However, the vacuolization that chiefly characterizes the morphology of neurons in spongiform encephalopathy might constitute a physical disruption with subsequent rapidly progressive impairment of maintenance of homeostatic viability of neurons due to precisely loss of membrane integrity of the plasmalemma and cell organelles. As far as transmission of the prion particle is concerned, it would appear that active incorporation of this agent under the direction of the affected neuronal cell itself would implicate host attributes as paramount factors determining not only susceptibility to the pathologic effects of the prion particle but also to the mode of such infliction as arising in and constituting spongiform encephalopathy beyond its acquisition and progression. As a single set of acquired circumstances determining both transmissibility and also pathologic lesion creation, the spongiform neuronal change might arise directly from a membrane abnormality of water ingress and egress in and out of the neuron. An excess of water ingress intra-neuronally might actually constitute a phenomenon of active lesion induction even in terms simply of biophysical stress intra-neuronally. In simple terms, an understanding of pathogenesis in spongiform encephalopathy might actually implicate aspects of transmissibility as direct attributes of processes of template replication within a system of utilization and elimination of the prion particle. Indeed, susceptibility to spongiform change might constitute one aspect of a biologic process that arises from conformational change of the prion protein molecule that would in turn result from variable polymorphisms in modes of reactive handling of PrPc and PrPsc by the neurons and other constituent cell elements in the central nervous system.