Early distribution of radioactive liposomes and scrapie infectivity in mouse tissues following administration by different routes

Millson, G.C.; Kimberlin, R.H.; Manning, Elizabeth; Collis, Susan C.

doi:10.1016/0378-1135(79)90045-2

Cited by 44 publications

(28 citation statements)

References 16 publications

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“…A study of the routing of i.p. injected inoculum with radiolabelled liposomes indicated that 40~ of the label was retained for at least 30 min in the peritoneum (Millson et al, 1979).…”

Section: Resultsmentioning

confidence: 99%

Prolongation of Scrapie Incubation Period by an Injection of Dextran Sulphate 500 within the Month Before or After Infection

Farquhar

Dickinson

1986

Journal of General Virology

125

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“…A study of the routing of i.p. injected inoculum with radiolabelled liposomes indicated that 40~ of the label was retained for at least 30 min in the peritoneum (Millson et al, 1979).…”

Section: Resultsmentioning

confidence: 99%

Prolongation of Scrapie Incubation Period by an Injection of Dextran Sulphate 500 within the Month Before or After Infection

Farquhar

Dickinson

1986

Journal of General Virology

125

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“…Many of these studies dealt with questions concerning the mechanism of neuroinvasion and the factors controlling it for different scrapie agents and for a variety of injection routes. Previous studies on the haematogenous spread of scrapie have been performed and its role in the neuropathogenesis of the disease has been discussed (Manuelidis et al, 1978;Millson et al, 1979;Kuroda et al, 1983;Diringer, 1984). There is ample evidence suggesting that scrapieinduced pathogenesis is due to neural spread of infectivity (Buyukmihci et al, 1980(Buyukmihci et al, , 1983Fraser, 1982;Kimberlin & Walker 1980, 1986.…”

Section: Discussionmentioning

confidence: 99%

Further characterization of scrapie replication in PC12 cells

Rubenstein

Scalici

Papini

et al. 1990

Journal of General Virology

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The rat pheochromocytoma cell line, PC 12, undergoes neuron-like morphological, biochemical and electrophysiological differentiation, in the presence of low concentrations of nerve growth factor (NGF). NGFtreated PC12 cells have been shown previously to support 139A scrapie agent replication. In the present report we extended these findings and analysed the cellular conditions necessary for agent replication. Following the infection of differentiated PC12 cells, scrapie replicated to relatively high titres as determined by an incubation period assay. The removal of NGF, which causes the gradual dedifferentiation of PC12 cells, resulted in the inability of scrapie to replicate. The scrapie infectivity detected in PC 12 cultures is cellassociated and not released into the medium. Cells in infected cultures did not show any change in morphology when compared to cells in mock-infected cultures. Titration studies of scrapie infectivity in PC12 cells have indicated that up to 4 LDso units per cell can be obtained although a yield of 1 LD50 per cell was more common. Using an approximate m.o.i, of 1, only differentiated PC 12 cells supported 139A scrapie agent replication when compared to two other differentiated, neuronal cell types, indicating that PC12 cells are more susceptible to agent replication. These studies support further the suitability of using differentiated PC 12 cells as an in vitro model to study scrapie agent replication.

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“…A primary viraemia has been shown to occur with 139A scrapie in CW mice which can account for the initial spread of infection to spleen etc., but it was not detectable later (Millson et al, 1979). Recently, more sensitive methods have been used to show a viraemic phase in hamsters which lasted for at least 40 days after the i.p.…”

Section: Discussionmentioning

confidence: 99%

Pathogenesis of Scrapie (Strain 263K) in Hamsters Infected Intracerebrally, Intraperitoneally or Intraocularly

Kimberlin¹,

Walker

1986

Journal of General Virology

197

118

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SUMMARYAfter intracerebral (i.c.) infection of hamsters, the 263K strain of scrapie replicated at a nearly constant exponential rate until clinical disease developed when titres in brain averaged 9.8 log10 LDs0 i.c. units/g. After intraperitoneal infection, scrapie replication was first detected in spleen, then in thoracic spinal cord and finally in lumbar cord and brain. This pattern suggests that invasion of the central nervous system occurs by spread of infection along certain visceral autonomic nerves. Infectivity was detected in the thoracic cord only 3 to 4 weeks after infection (incubation period 16 weeks) indicating the exceptional neuroinvasiveness of this scrapie model. This observation and the failure of splenectomy to lengthen incubation period raises the possibility of direct infection of nerve tissue in the peritoneum and transport to the thoracic cord with minimal prior replication of scrapie agent extraneurally. After intraocular infection of the right eye, replication (or accumulation) of scrapie was detected in the right optic nerve and left superior colliculus, then in the right superior colliculus and finally in the left optic nerve and medulla. This pattern shows that scrapie infection can spread along nerves, possibly by intra-axonal transport. The duration of agent replication in brain (between detectable onset of replication and clinical disease) was shortest after intraperitoneal infection (51 to 58 days), longer after intracerebral infection (81 to 88 days) and longest after intraocular infection (> 121 days). These differences may reflect the relative efficiency of the neural pathways by which infectivity spreads from different sites of entry in the brain to the postulated 'clinical target areas'.

show abstract

Early distribution of radioactive liposomes and scrapie infectivity in mouse tissues following administration by different routes

Cited by 44 publications

References 16 publications

Prolongation of Scrapie Incubation Period by an Injection of Dextran Sulphate 500 within the Month Before or After Infection

Prolongation of Scrapie Incubation Period by an Injection of Dextran Sulphate 500 within the Month Before or After Infection

Further characterization of scrapie replication in PC12 cells

Pathogenesis of Scrapie (Strain 263K) in Hamsters Infected Intracerebrally, Intraperitoneally or Intraocularly

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