Tubulovesicular structures (particles; TVS) are virion-like particles 25?30 nm in diameter found by thin-section electron microscopy in brains of all prion diseases including scrapie, Creutzfeldt-Jakob disease (CJD), fatal familial insomnia (FFI) and Gerstmann-Str?ussler-Scheineker disease (GSS), as well as in cell cultures infected with TSE agents. TVS are regarded as a disease-specific ultrastructural marker for TSEs and, by those not completely satisfied with the prion hypothesis, they are even considered to be a possible candidate for the infectious TSE agent itself. A caveat regarding that interpretation stemmed from previous failures to find TVS by electron microscopic studies of tissues from animals infected with the Echigo-1 strain of CJD agent. We now report detecting TVS in brains of hamsters infected with that strain of CJD agent, albeit with a very low frequency.
Tubulovesicular structures (particles ? TVS) are the only ultrastructural marker for all prion diseases as seen by thin-section electron microscopy as opposed to ?negative-staining' techniques. TVS are spheres or short rods of approximately 27 nm in diameter. That size of TVS is also the size of filter cut-off of infectivity as judged from the ultrafiltration studies and the size of the smallest infectious unit as recently estimated. TVS have been found in all naturally occurring and experimentally induced prion diseases, including variant Creutzfeldt-Jakob disease and human familial TSEs ? fatal familial insomnia and Gerstmann-Str?ussler-Scheinker disease. In longitudinal studies, the number of neuronal processes containing TVS correlates roughly with the incubation period and with infectivity. Hence, they are readily found in hamsters infected with the 263K strain of scrapie but it is very difficult to find them in human TSEs where titer is lower. The composition of TVS is unknown but they are not composed of PrP. Their consistent presence in all TSEs suggests the unexplained role at least of TSE pathogenesis.