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Conserved properties of human and bovine prion strains on transmission to guinea pigs.

ABSTRACT: The first transmissions of human prion diseases to rodents used guinea pigs (Gps, Cavia porcellus). Later, transgenic mice expressing human or chimeric human/mouse PrP replaced Gps, but the small size of the mouse limits some investigations. To investigate the fidelity of strain-specific prion transmission to Gps, we inoculated 'type 1' and 'type 2' prion strains into Gps, and we measured the incubation times and determined the strain-specified size of the unglycosylated, protease-resistant (r) PrP(Sc) fragment. Prions passaged once in Gps from cases of sporadic (s) Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker (GSS) disease caused by the P102L mutation were used, as well as human prions from a variant (v) CJD case, bovine prions from bovine spongiform encephalopathy (BSE) and mouse-passaged scrapie prions. Variant CJD and BSE prions transmitted to all the inoculated Gps with incubation times of 367 ± 4 and 436 ± 28 days, respectively. On second passage in Gps, vCJD and BSE prions caused disease in 287 ± 4 and 310 ± 4 days, whereas sCJD and GSS prions transmitted in 237 ± 4 and 279 ± 19 days, respectively. Although hamster Sc237 prions transmitted to two of three Gps after 574 and 792 days, mouse-passaged RML and 301V prion strains, the latter derived from BSE prions, failed to transmit disease to Gps. Those Gps inoculated with vCJD or BSE prions exhibited 'type 2' unglycosylated, rPrP(Sc) (19 kDa), whereas those receiving sCJD or GSS prions displayed 'type 1' prions (21 kDa), as determined by western blotting. Such strain-specific properties were maintained in Gps as well as mice expressing a chimeric human/mouse transgene. Gps may prove particularly useful in further studies of novel human prions such as those causing vCJD.

SUBMITTER: Safar JG

PROVIDER: S-EPMC3164925 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Conserved properties of human and bovine prion strains on transmission to guinea pigs.

Safar Jiri G JG Giles Kurt K Lessard Pierre P Letessier Frederic F Patel Smita S Serban Ana A Dearmond Stephen J SJ Prusiner Stanley B SB

Laboratory investigation; a journal of technical methods and pathology 20110704 9

The first transmissions of human prion diseases to rodents used guinea pigs (Gps, Cavia porcellus). Later, transgenic mice expressing human or chimeric human/mouse PrP replaced Gps, but the small size of the mouse limits some investigations. To investigate the fidelity of strain-specific prion transmission to Gps, we inoculated 'type 1' and 'type 2' prion strains into Gps, and we measured the incubation times and determined the strain-specified size of the unglycosylated, protease-resistant (r) ...[more]

PMID: 21727894

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Project description:Ebola virus (EBOV) transmission is currently poorly characterized and is thought to occur primarily by direct contact with infectious material; however transmission from swine to nonhuman primates via the respiratory tract has been documented. To establish an EBOV transmission model for performing studies with statistical significance, groups of six guinea pigs (gps) were challenged intranasally (i.n.) or intraperitoneally (i.p.) with 10,000 times the 50% lethal dose (LD50) of gp-adapted EBOV, and naive gps were then introduced as cage mates for contact exposure at 1 day postinfection (p.i.). The animals were monitored for survival and clinical signs of disease and quantitated for virus shedding postexposure. Changes in the duration of contact of naive gps with infected animals were evaluated for their impact on transmission efficiency. Transmission was more efficient from i.n.- than from i.p.-challenged gps, with 17% versus 83% of naive gps surviving exposure, respectively. Virus shedding was detected beginning at 3 days p.i. from both i.n.- and i.p.-challenged animals. Contact duration positively correlated with transmission efficiency, and the abrogation of direct contact between infected and naive animals through the erection of a steel mesh was effective at stopping virus spread, provided that infectious animal bedding was absent from the cages. Histopathological and immunohistochemical findings show that i.n.-infected gps display enhanced lung pathology and EBOV antigen in the trachea, which supports increased virus transmission from these animals. The results suggest that i.n.-challenged gps are more infectious to naive animals than their systemically infected counterparts and that transmission occurs through direct contact with infectious materials, including those transported through air movement over short distances.Ebola is generally thought to be spread between humans though infectious bodily fluids. However, a study has shown that Ebola can be spread from pigs to monkeys without direct contact. Further studies have been hampered, because an economical animal model for Ebola transmission is not available. To address this, we established a transmission model in guinea pigs and determined the mechanisms behind virus spread. The survival data, in addition to microscopic examination of lung and trachea sections, show that mucosal infection of guinea pigs is an efficient model for Ebola transmission. Virus spread is increased with longer contact times with an infected animal and is possible without direct contact between an infected and a naive host but can be stopped if infectious materials are absent. These results warrant consideration for the development of future strategies against Ebola transmission and for a better understanding of the parameters involved in virus spread.

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Conserved properties of human and bovine prion strains on transmission to guinea pigs.

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Conserved properties of human and bovine prion strains on transmission to guinea pigs.

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