White-tailed deer are susceptible to the agent of sheep scrapie by intracerebral inoculation

ABSTRACT The presence of the prion agent in skeletal muscle is thought to be due to the infection of nerve fibers located within the muscle. We report here that the pathological isoform of the prion protein, PrPSc, accumulates within skeletal muscle cells, in addition to axons, in the tongue of hamsters following intralingual and intracerebral inoculation of the HY strain of the transmissible mink encephalopathy agent. Localization of PrPSc to the neuromuscular junction suggests that this synapse is a site for prion agent spread between motor axon terminals and muscle cells. Following intracerebral inoculation, the majority of PrPSc in the tongue was found in the lamina propria, where it was associated with sensory nerve fibers in the core of the lingual papillae. PrPSc staining was also identified in the stratified squamous epithelium of the lingual mucosa. These findings indicate that prion infection of skeletal muscle cells and the epithelial layer in the tongue can be established following the spread of the prion agent from nerve terminals and/or axons that innervate the tongue. Our data suggest that ingestion of meat products containing prion-infected tongue could result in human exposure to the prion agent, while sloughing of prion-infected epithelial cells at the mucosal surface of the tongue could be a mechanism for prion agent shedding and subsequent prion transmission in animals.

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A COMPARATIVE STUDY OF RECENTLY ISOLATED HUMAN STRAINS AND A PASSAGE STRAIN OF POLIOMYELITIS VIRUS

Journal of Experimental Medicine ◽

10.1084/jem.58.5.513 ◽

1933 ◽

Vol 58 (5) ◽

pp. 513-529 ◽

Cited By ~ 16

Author(s):

John R. Paul ◽

James D. Trask

Keyword(s):

Comparative Study ◽

Human Strain ◽

Time Interval ◽

Subsequent Infection ◽

Poliomyelitis Virus ◽

Intracerebral Inoculation ◽

Human Sera ◽

Cross Immunity ◽

Experimental Disease

1. Confirmation of the qualitative differences which exist between so called human and passage strains of poliomyelitis virus has been established by the following observations. (a) The experimental disease induced by two human strains usually failed to protect monkeys against a subsequent infection by a passage strain, and in the few instances in which the reverse experiment could be tried a similar lack of protection was observed. (b) In some human sera the neutralizing power for a human strain differed qualitatively from the neutralizing power for a passage strain. 2. The time interval between the intracerebral inoculation of heterologous strains has been found to be an important factor bearing upon the results of the reinoculation experiments reported. Within the intervals used, the greater the period between the original infection and the reinoculation with a heterologous strain, the less was the degree of cross-immunity observed.

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Gene expression analysis in distinct regions of the central nervous system during the development of SSBP/1 sheep scrapie

Veterinary Microbiology ◽

10.1016/j.vetmic.2010.05.043 ◽

2011 ◽

Vol 147 (1-2) ◽

pp. 42-48 ◽

Cited By ~ 3

Author(s):

Anton G. Gossner ◽

Jim D. Foster ◽

John K. Fazakerley ◽

Nora Hunter ◽

John Hopkins

Keyword(s):

Gene Expression ◽

Central Nervous System ◽

Nervous System ◽

Expression Analysis ◽

Gene Expression Analysis ◽

The Central Nervous System ◽

Sheep Scrapie

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FURTHER STUDIES CONCERNING THE FILTRABLE VIRUS PRESENT IN THE SUBMAXILLARY GLANDS OF GUINEA PIGS

Journal of Experimental Medicine ◽

10.1084/jem.46.6.935 ◽

1927 ◽

Vol 46 (6) ◽

pp. 935-956 ◽

Cited By ~ 17

Author(s):

Ann G. Kuttner

Keyword(s):

Guinea Pig ◽

Guinea Pigs ◽

Active Material ◽

Active Agent ◽

Submaxillary Gland ◽

Intracerebral Inoculation ◽

Submaxillary Glands ◽

Direct Inoculation ◽

In Series ◽

Subcutaneous Inoculation

1. It has been shown that the guinea pig virus localizes in the submaxillary glands of young guinea pigs following subcutaneous, intraperitoneal, or intravenous injection of active material, and that the specific lesion is demonstrable in the glands in 12 to 15 days. When an active infection of the gland has been produced in this way, the guinea pigs are refractory to intracerebral inoculation of the virus. 2. No lesion develops in the submaxillary glands of young guinea pigs injected subcutaneously with guinea pig virus which has been inactivated by heat. Young guinea pigs which have received injections of heat-killed virus do not become refractory to intracerebral inoculation of the virus. 3. When young guinea pigs from which both submaxillary glands have been removed are injected subcutaneously with active virus, the virus localizes in the parotid gland, and the animals become refractory to intracerebral inoculation. 4. It has been impossible to demonstrate virucidal properties in the sera of adult guinea pigs which have become spontaneously infected with the virus, or in the sera of young guinea pigs which have been artificially rendered refractory to intracerebral inoculation. 5. It has been possible to transmit the virus from guinea pig to guinea pig continuously in series through seven animals by direct inoculation from submaxillary gland to submaxillary gland. 6. The fact that the virus regularly localizes in the submaxillary glands following subcutaneous inoculation has been utilized in passing the virus from guinea pig to guinea pig. 2 weeks after the subcutaneous inoculation of the virus into young guinea pigs, the active agent was present in the submaxillary glands. Emulsions of the submaxillary glands of these animals were then used for the subcutaneous injection of another group of young guinea pigs. In this way the virus was transmitted continuously from skin to submaxillary gland through a series of seven animals.

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SURVIVAL OF POLIOMYELITIC VIRUS IN THE BRAIN OF THE RABBIT

Journal of Experimental Medicine ◽

10.1084/jem.27.3.443 ◽

1918 ◽

Vol 27 (3) ◽

pp. 443-447 ◽

Cited By ~ 3

Author(s):

Harold L. Amoss

Keyword(s):

Intracranial Pressure ◽

Pressure Effects ◽

Rabbit Brain ◽

High Dilution ◽

Increased Intracranial Pressure ◽

Intracerebral Inoculation ◽

Pathological Lesions ◽

Active Virus ◽

The Brain

Suspensions of the central nervous tissues of monkeys, containing the active filterable virus of poliomyelitis, may be injected into the brain of rabbits without setting up symptoms, provided the volume of injection does not cause dangerous increased intracranial pressure. Aside from the pressure effects which develop quickly, no other symptoms or pathological lesions are produced by the suspensions. The active virus of poliomyelitis survives in the brain of rabbits for 4 days, as determined by tests in the monkey, into which the excised site of injection in the rabbit brain is reinoculated. It cannot be detected by this test after the expiration of 7 days. The virus of poliomyelitis is unadapted to the rabbit, and neither induces lesions nor survives long in the central nervous organs of that animal. In this respect it differs from certain streptococci cultivated from poliomyelitic tissues. A monkey immunized to streptococcus cultivated from human poliomyelitic nervous tissues yielded a serum which agglutinated the streptococcus in high dilution, but was without neutralizing action on the filtered virus; and the streptococcus-immune monkey was not protected against the effects of an intracerebral inoculation of the filtered virus. The experiments recorded provide additional reasons for concluding that the streptococcus cultivated from cases of poliomyelitis differs essentially from the filterable virus and is not the microbic cause of epidemic poliomyelitis.

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Characterization of the specific meningeal T cell response to intracerebral inoculation of Theiler's murine encephalomyelitis virus

Journal of Neuroimmunology ◽

10.1016/0165-5728(91)90044-8 ◽

1991 ◽

Vol 31 (3) ◽

pp. 229-234

Author(s):

Ann-Karolin Scheu ◽

Nazario Rubio

Keyword(s):

T Cell ◽

Cell Response ◽

T Cell Response ◽

Theiler's Murine Encephalomyelitis Virus ◽

Intracerebral Inoculation ◽

Theiler’S Murine Encephalomyelitis Virus ◽

Encephalomyelitis Virus

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Search for a Prion-Specific Nucleic Acid

Journal of Virology ◽

10.1128/jvi.79.16.10796-10806.2005 ◽

2005 ◽

Vol 79 (16) ◽

pp. 10796-10806 ◽

Cited By ~ 91

Author(s):

Jiri G. Safar ◽

Klaus Kellings ◽

Ana Serban ◽

Darlene Groth ◽

James E. Cleaver ◽

...

Keyword(s):

Nucleic Acid ◽

Nucleic Acids ◽

Uv Irradiation ◽

Syrian Hamsters ◽

Variable Sequence ◽

Intracerebral Inoculation ◽

Prion Infectivity ◽

Prion Strains ◽

Rapid Clearance

ABSTRACT Diversity of prion strains was attributed to an elusive nucleic acid, yet a search spanning nearly two decades has failed to identify a prion-specific polynucleotide. In our search for a prion-specific nucleic acid, we analyzed nucleic acids in purified fractions from the brains of Syrian hamsters infected with Sc237 prions. Purification of Sc237 prions removed nucleic acids larger than 50 nucleotides as measured by return refocusing electrophoresis (RRGE). To determine the size of the largest polynucleotide present in purified fractions at an abundance of one molecule per infectious (ID50) unit, we measured prions present after inoculation. In order to account for the rapid clearance of prions after intracerebral inoculation, we determined the number of PrPSc molecules and ID50 units of prions that were retained in brain. Factoring in clearance after inoculation, we estimate that the largest polynucleotide present in our purified fractions at one molecule per ID50 unit is ≈25 nucleotides in length. In the same fractions, there were ≈3,000 protease-resistant PrPSc molecules per ID50 unit after accounting for clearance of PrPSc following inoculation. We compared the resistance of Sc237 and 139H prions to inactivation by UV irradiation at 254 nm. Irradiation of homogenates and microsomes diminished prion infectivity by a factor of ≈1,000 but did not alter the strain-specified properties of the Sc237 and 139H prions. The data reported here combined with the production of synthetic prions argue that the 25-mer polynucleotides found in purified prion preparations are likely to be host encoded and of variable sequence; additionally, these 25-mers are unlikely to be prion specific.

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