No abstract

Simian foamy virus (SFV) type 6, originally isolated from the kidney of a kuru-inoculated chimpanzee, has been adapted to produce an asymptomatic infection in Swiss-Webster white mice, with virus detected in the kidney and spleen for up to 10 months after intra-peritoneal inoculation, and the presence in some animals of complement-fixing, but not neutralizing, serum antibody. This first successful experimental infection of the laboratory mouse by a representative of the foamy virus group has special interest as a convenient model in which to study pathogenesis and viral latency, particularly in view of the isolation and recent characterization of a foamy virus from human tissue which is virtually indistinguishable from the SFV type 6 used in the present study.

Golden Syrain hamsters were inoculated intracerebrally with the hamster-adapted 263K strain of scrapie virus, and the evolution of in vitro cell fusing activity induced by brain suspensions was compared with brain infectivity titers and histological changes. Cell-fusing activity abruptly appeared 4 weeks after inoculation, 1 week before the earliest detectable histopathological changes, at an infectivity level of 7.6 log 50% lethal doses per g of brain. Cell-fusing activity was sustained throughout the remaining 4 weeks of the incubation period and the subsequent 1- to 3-week stage of clinical illness but did not increase with the logarithmic progression of infectivity, which reached a level of 11 log 50% lethal doses per g in the agonal stage of disease. Gliosis was most sensitively detected by a monoclonal antibody reacting with astrocyte intermediate filaments in an indirect immunofluorescence test, anticipating histological recognition of gliosis and spongiform change by 1 to 2 weeks. In vitro cell-fusing activity is thus one of the earliest known biological markers (apart from infectivity itself) of experimental scrapie infection.

In vitro cell-fusing activity of brain suspensions prepared from patients with Alzheimer disease occurred in 10 of 17 familial cases (59%), a level similar to that seen in transmissible Creutzfeldt-Jakob disease (CJD), but in only 3 of 17 sporadic cases (17%), a level not statistically different from that in nonneurologic control patients. This biologic distinction between the familial and sporadic forms of Alzheimer disease may be related to the previously reported transmission to primates of a CJD-like disease from two familial cases of Alzheimer disease.

In vitro cell-fusing activity of brain suspensions from 33 patients with transmissible cases of Creutzfeldt-Jakob disease (CJD) was compared to activity of brains from 26 patients with a variety of other degenerative neurological diseases, and with activity of brains from 25 patients without neurological disease. A significantly higher proportion of CJD brains ( 61 %) was positive than other neurologically diseased brains (31-35%) or the brains without neurological disease (0-4%).Although not yet sufficiently specific to be useful as a diagnostic test for human CJD, the assay nevertheless opens a line of investigation into the pathophysiology of degenerative neurological diseases and could prove immediately useful in rapidly locating material of maximum interest in purification procedures for experimental spongiform encephalopathy virus.