Summary
The current study focused on the role of lymphoid elements of the lymphoreticular system in scrapie pathogenesis. In the first experiment, adherent and non-adherent splenocytes from mice infected with the 139A scrapie strain were prepared. The level of infectivity on a per cell basis was significantly higher in the adherent cell population. In a second set of experiments, thymocytes, unfractionated splenocytes, T-cell enriched and T-cell depleted fractions of splenocytes were infected in vitro with ME7 scrapie strain. There was no evidence of replication of scrapie in ME7-exposed cells in any of the preparations during the first 5–14 days post-exposure. In assays done 5 days after infection, most of the infectivity was cell-associated. These data suggest that lymphoid cells are not involved in scrapie replication. The level of IgA in the serum of 139A-infected mice was markedly reduced compared to the levels in mice injected with normal mouse brain homogenate or with the ME7 scrapie strain. The reduction in IgA levels in 139A-infected mice was evident at each of the 4 time points tested. The final experiment dealt with the question of scrapie replication in the lymphoreticular organs in mouse strains with different incubation periods for 139A after intraperitoneal injection. The results in this experiment suggest that the difference in incubation periods is related to differences in time of access of infection to the central nervous system rather than to differences in the ability of agent to replicate in spleen.
Similar content being viewed by others
References
Bruce ME (1985) Agent replication dynamics in a long incubation period model of mouse scrapie. J Gen Virol 66: 2517–2522
Carp RI, Callahan SM (1981) In vitro interaction of scrapie agent and mouse peritoneal macrophages. Intervirology 16: 8–13
Carp RI, Callahan SM (1982) Effect of mouse peritoneal macrophages on scrapie infectivity during extended in vitro incubation. Intervirology 17: 201–207
Carp RI, Callahan SM (1985) Effect of prior treatment with thioglycolate on the incubation period of intraperitoneally injected scrapie. Intervirology 24: 170–173
Carp RI, Callahan SM (1986) Scrapie incubation periods and end-point titers in mouse strains differing at the H-2D locus. Intervirology 26: 85–92
Carp RI, Callahan SM (1991) Variation in the characteristics of ten mouse-passaged scrapie lines derived from five scrapie-positive sheep. J Gen Virol 72: 293–298
Carp RI, Callahan SM, Sersen EA, Moretz, RC (1984) Preclinical changes in weight of scrapie-infected mice as a function of scrapie agent-mouse strain combination. Intervirology 21: 61–69
Carp RI, Kascsak RJ, Wisniewski HM, Merz PA, Rubenstein R, Bendheim P, Bolton D (1989) The nature of the scrapie agent remains a puzzle. Alzheimer Dis Assoc Disord 3: 79–99
Carp RI, Kim YS, Kascsak RJ, Merz PA, Rubenstein R (1989) Classic genetics of scrapie In: Iqbal K, Wisniewski HM, Winblad B (eds) Alzheimers disease and related disorders. Alan R. Liss, New York, pp 567–582
Carp RI, Merz PA, Moretz RC, Somerville RA, Callahan SM, Wisniewski HM (1985) Biological properties of scrapie: an unconventional slow virus. In: Maramorosch K, McKelvey JJ (eds) Subviral pathogens of plants and animals: viroids and prions. Academic Press, New York, pp 425–464
Carp RI, Rubenstein R (1991) Diversity and significance of scrapie strains. Semin Virol 2: 203–213
Clarke MC, Haig DA (1971) Multiplication of scrapie agent in mouse spleen. Res Vet Sci 12: 195–197
Clarke MC, Kimberlin RH (1984) Pathogenesis of mouse scrapie: distribution of agent in the plup and stroma of infected spleen. Vet Microbiol 9: 215–225
Collis SC, Kimberlin RH (1985) Long-term persistence of scrapie infection in mouse spleens in the absence of clinical disease. FEMS Microbiol Lett 29: 111–114
Collis SC, Kimberlin RH (1989) Polyclonal increase in certain IgG subclasses in mice persistently infected with the 87V strain of scrapie. J Comp Pathol 101: 131–141
Collis SC, Kimberlin RH (1993) Further studies on changes in immunoglobulin G in the sera and CSF of Herdwich sheep with natural and experimental scrapie. J Comp Pathol 93: 331–338
Collis SC, Kimberlin RH, Millson GC (1979) Immunoglobulin G concentrations in the sera of Herdwick sheep with natural scrapie. J Comp Pathol 89: 389–396
Dickinson AG (1976) Scrapie in sheep and goats. In: Kimberlin R (ed) Slow virus diseases of animals and man. North-Holland, Amsterdam, pp 209–241
Dickinson AG, Fraser H (1972) Scrapie: effect of Dh gene on incubation period of extraneurally injected agent. Heredity 29: 91–93
Eklund CM, Kennedy RC, Hadlow WJ (1967) Pathogenesis of scrapie virus infection in the mouse. J Infect Dis 117: 15–22
Fraser H, Dickinson AG (1970) Pathogenesis of scrapie in the mouse: the role of the spleen. Nature 226: 462–463
Fraser H, Farquhar CF (1987) Ionising radiation has no influence on scrapie incubation period in mice. Vet Microbiol 13: 211–223
Fraser H, Davies D, McConnell I, Farquhar CF (1988) Are radiation-resistant, post-miotic, long-lived (RRPMLL) cells involved in scrapie replication? In: Court LA, Cathala F (eds) II Symposium International sur les Virus Non Conventionnels du Systeme Nerveux Central. Commissariat a I'Energie Atomique, Departement de Protection Sanitaire, Service de Documentation, Fontenay-aux-Roses, Cedex, pp 563–574
Gajdusek DC (1977) Unconventional viruses and the origin and disappearance of kuru. Science 197: 943–960
Julius MH, Simpson E, Herzenberg LA (1973) A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol 3: 645–649
Kim YS, Carp RI, Callahan SM, Natelli M, Wisniewski HM (1990) Vacuolization, incubation period and survival time analyses in three mouse genotypes injected stereotaxically in three brain regions with the 22L scrapie strain. J Neuropathol Exp Neurol 49: 106–113
Kim YS, Carp RI, Callahan SM, Wisniewski HM (1987) Incubation periods and survival times for mice injected stereotaxically with three scrapie strains in different brain regions. J Gen Virol 68: 695–702
Kim YS, Carp RI, Callahan SM, Wisniewski HM (1988) Adrenal involvement in scrapie induced obesity. Proc Soc Exp Biol Med 189: 21–27
Kim YS, Carp RI, Callahan SM, Wisniewski HM (1990) Incubation periods and histopathological changes in mice injected stereotaxically in different brain areas with the 87V scrapie strain. Acta Neuropathol 80: 389–392
Kimberlin RH, Walker CA (1979) Pathogenesis of mouse scrapie: dynamics of agent replication in spleen, spinal cord and brain after infection by different routes. J Comp Pathol 89: 551–562
Kimberlin RH, Walker CA (1980) Pathogenesis of mouse scrapie: evidence for neural spread of infection to the CNS. J Gen Virol 51: 183–187
Kimberlin RH, Walker CA (1982) Pathogenesis of mouse scrapie: patterns of agent replication in different parts of the CNS following intraperitoneal infection. J Roy Soc Med 75: 618–624
Kimberlin RH, Walker CA (1986) Pathogenesis of scrapie (strain 263K) in hamsters infected intracerebrally, intraperitoneally or intraocularly. J Gen Virol 67: 255–263
Kimberlin RH, Walker CA (1986) Suppression of scrapie infection in mice by heteropolyanion 23, dextran sulfate, and some other polyanions. Antimicrob Agents Chemother 30: 409–413
Kimberlin RH, Walker CA (1988) Pathogenesis of experimental scrapie. In: Bock G, Marsh J (eds) Novel infectious agents and the central nervous system. J. Wiley, Chichester, pp 37–62
Kimberlin RH, Walker CA (1989) The role of the spleen in the neuroinvasion of scrapie in mice. Virus Res 12: 201–212
Kimberlin RH, Walker CA (1990) Intraperitoneal infection with scrapie is established within minutes of infection and is non-specifically enhanced by a variety of different drugs. Arch Virol 112: 103–114
Kitamoto T, Muramoto T, Mohri S, Doh-Ura K, Tateishi J (1991) Abnormal isoform of prion protein accumulates in follicular dendritic cells in mice with Creutzfeldt-Jakob disease. J Virol 65: 6292–6295
Kuroda Y, Gibbs CJ Jr, Amyx HL, Gajdusek DC (1983) Creutzfeldt-Jakob disease in mice: persistent viremia and preferential replication of virus in low-density lymphocytes. Infect Immun 41: 154–161
Lavelle GC, Sturman L, Hadlow WJ (1972) Isolation from mouse spleen of cell populations with high specific infectivity for scrapie virus. Infect Immun 5: 319–323
Mancini C, Carbonara AO, Heremans JF (1965) Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry 2: 235–254
McBride PA, Eikelenboom P, Kraal G, Fraser H, Bruce ME (1992) PrP protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie-infected mice. J Pathol 168: 413–418
Rodgers B, Mims CA (1981) Interaction of influenza virus with mouse macrophages. Infect Immun 31: 751–757
Robinson MM, Gorham JR (1990) Pathogenesis of hamster scrapie. Adherent splenocytes are associated with relatively high levels of infectivity. Arch Virol 112: 283–289
Sigurdsson SB (1954) Rida, a chronic encephalitis of sheep with general remarks on infections which develop slowly and some of their special characteristics. Br Vet J 110: 341–354
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Carp, R.I., Callahan, S.M., Patrick, B.A. et al. Interaction of scrapie agent and cells of the lymphoreticular system. Archives of Virology 136, 255–268 (1994). https://doi.org/10.1007/BF01321056
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01321056