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Characteristics of 263K scrapie agent in multiple hamster species.

Meade-White KD, Barbian KD, Race B, Favara C, Gardner D, Taubner L, Porcella S, Race R - Emerging Infect. Dis. (2009)

Bottom Line: Transmissible spongiform encephalopathy (TSE) diseases are known to cross species barriers, but the pathologic and biochemical changes that occur during transmission are not well understood.To better understand these changes, we infected 6 hamster species with 263K hamster scrapie strain and, after each of 3 successive passages in the new species, analyzed abnormal proteinase K (PK)-resistant prion protein (PrPres) glycoform ratios, PrPres PK sensitivity, incubation periods, and lesion profiles.Furthermore, 2 polymorphic regions of the prion protein amino acid sequence correlated with profile differences in these TSE-infected hamster species.

View Article: PubMed Central - PubMed

Affiliation: National Institute of Allergy and Infectious Diseases, Hamilton, Montana, USA. kmeade-white@niaid.nih.gov

ABSTRACT
Transmissible spongiform encephalopathy (TSE) diseases are known to cross species barriers, but the pathologic and biochemical changes that occur during transmission are not well understood. To better understand these changes, we infected 6 hamster species with 263K hamster scrapie strain and, after each of 3 successive passages in the new species, analyzed abnormal proteinase K (PK)-resistant prion protein (PrPres) glycoform ratios, PrPres PK sensitivity, incubation periods, and lesion profiles. Unique 263K molecular and biochemical profiles evolved in each of the infected hamster species. Characteristics of 263K in the new hamster species seemed to correlate best with host factors rather than agent strain. Furthermore, 2 polymorphic regions of the prion protein amino acid sequence correlated with profile differences in these TSE-infected hamster species.

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A) Proteinase K–resistant prion protein (PrPres) pathogenicity profiles in Syrian hamsters inoculated with third-passage PrPres. B) Hematoxylin and eosin (H&E)–stained lesion profiles of Syrian hamsters inoculated with brain homogenate derived from third-passage hamsters. Each point represents the average from 6 different animals scored in the following areas: 1, cerebellum; 2, posterior colliculus; 3, superior colliculus; 4, brain stem; 5, spinal cord; 6, thalamus; 7, hypothalamus; 8, hippocampus; 9, cortex; 10, olfactory bulbs; 11, caudate putamen; 12, septal nucleus; 13, tegmentum. Syrian hamster inoculated with third-passage brain homogenate from the following hamster species: ●, Turkish; ■, Djungarian; ♦, Chinese; ▼, Armenian; ▲, Siberian; □, Syrian. Arrows represent differences in multiple regions indicating increases or decreases in vacuolation or PrPres deposition.
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Figure 6: A) Proteinase K–resistant prion protein (PrPres) pathogenicity profiles in Syrian hamsters inoculated with third-passage PrPres. B) Hematoxylin and eosin (H&E)–stained lesion profiles of Syrian hamsters inoculated with brain homogenate derived from third-passage hamsters. Each point represents the average from 6 different animals scored in the following areas: 1, cerebellum; 2, posterior colliculus; 3, superior colliculus; 4, brain stem; 5, spinal cord; 6, thalamus; 7, hypothalamus; 8, hippocampus; 9, cortex; 10, olfactory bulbs; 11, caudate putamen; 12, septal nucleus; 13, tegmentum. Syrian hamster inoculated with third-passage brain homogenate from the following hamster species: ●, Turkish; ■, Djungarian; ♦, Chinese; ▼, Armenian; ▲, Siberian; □, Syrian. Arrows represent differences in multiple regions indicating increases or decreases in vacuolation or PrPres deposition.

Mentions: To determine the respective contributions of the agent and host in immunohistochemical patterns, we injected brain homogenate from third-passage hamsters back into Syrian hamsters. When patterns were compared with those of 263K Syrian hamster, only a few differences from 263K Syrian were observed. Specifically, less PrPres was deposited in the posterior colliculus (region 2) in Syrian hamsters inoculated with brain homogenate from Chinese hamsters, and more PrPres was deposited in the thalamus (region 6) of Syrian hamsters inoculated with brain homogenate from Djungarian hamsters (Figure 6, panel A). We also observed a decrease in vacuolation in the hippocampus (region 8) and cortex (region 9) of Syrian hamsters inoculated with brain homogenate from Chinese hamsters (Figure 6, panel B). For all other hamster species inocula, no remarkable differences from 263K Syrian hamster were noted. Therefore, the host appeared to play an important role in determining immunohistochemical patterns. It is not known whether the differences seen in the Chinese and Djungarian hamsters are due to donor species effect (27,28), whereby a temporary change occurs as an agent is passed through a new host species, or whether selection of a new strain has occurred. To answer this question, a second passage through Syrian hamsters is needed. These results suggest that although 263K agent was substantially altered by passage through the new hamster species, in general it was not able to impart molecular characteristics like glycoform or the pathologic patterns established in the new species back to the Syrian hamsters.


Characteristics of 263K scrapie agent in multiple hamster species.

Meade-White KD, Barbian KD, Race B, Favara C, Gardner D, Taubner L, Porcella S, Race R - Emerging Infect. Dis. (2009)

A) Proteinase K–resistant prion protein (PrPres) pathogenicity profiles in Syrian hamsters inoculated with third-passage PrPres. B) Hematoxylin and eosin (H&E)–stained lesion profiles of Syrian hamsters inoculated with brain homogenate derived from third-passage hamsters. Each point represents the average from 6 different animals scored in the following areas: 1, cerebellum; 2, posterior colliculus; 3, superior colliculus; 4, brain stem; 5, spinal cord; 6, thalamus; 7, hypothalamus; 8, hippocampus; 9, cortex; 10, olfactory bulbs; 11, caudate putamen; 12, septal nucleus; 13, tegmentum. Syrian hamster inoculated with third-passage brain homogenate from the following hamster species: ●, Turkish; ■, Djungarian; ♦, Chinese; ▼, Armenian; ▲, Siberian; □, Syrian. Arrows represent differences in multiple regions indicating increases or decreases in vacuolation or PrPres deposition.
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Related In: Results  -  Collection

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Figure 6: A) Proteinase K–resistant prion protein (PrPres) pathogenicity profiles in Syrian hamsters inoculated with third-passage PrPres. B) Hematoxylin and eosin (H&E)–stained lesion profiles of Syrian hamsters inoculated with brain homogenate derived from third-passage hamsters. Each point represents the average from 6 different animals scored in the following areas: 1, cerebellum; 2, posterior colliculus; 3, superior colliculus; 4, brain stem; 5, spinal cord; 6, thalamus; 7, hypothalamus; 8, hippocampus; 9, cortex; 10, olfactory bulbs; 11, caudate putamen; 12, septal nucleus; 13, tegmentum. Syrian hamster inoculated with third-passage brain homogenate from the following hamster species: ●, Turkish; ■, Djungarian; ♦, Chinese; ▼, Armenian; ▲, Siberian; □, Syrian. Arrows represent differences in multiple regions indicating increases or decreases in vacuolation or PrPres deposition.
Mentions: To determine the respective contributions of the agent and host in immunohistochemical patterns, we injected brain homogenate from third-passage hamsters back into Syrian hamsters. When patterns were compared with those of 263K Syrian hamster, only a few differences from 263K Syrian were observed. Specifically, less PrPres was deposited in the posterior colliculus (region 2) in Syrian hamsters inoculated with brain homogenate from Chinese hamsters, and more PrPres was deposited in the thalamus (region 6) of Syrian hamsters inoculated with brain homogenate from Djungarian hamsters (Figure 6, panel A). We also observed a decrease in vacuolation in the hippocampus (region 8) and cortex (region 9) of Syrian hamsters inoculated with brain homogenate from Chinese hamsters (Figure 6, panel B). For all other hamster species inocula, no remarkable differences from 263K Syrian hamster were noted. Therefore, the host appeared to play an important role in determining immunohistochemical patterns. It is not known whether the differences seen in the Chinese and Djungarian hamsters are due to donor species effect (27,28), whereby a temporary change occurs as an agent is passed through a new host species, or whether selection of a new strain has occurred. To answer this question, a second passage through Syrian hamsters is needed. These results suggest that although 263K agent was substantially altered by passage through the new hamster species, in general it was not able to impart molecular characteristics like glycoform or the pathologic patterns established in the new species back to the Syrian hamsters.

Bottom Line: Transmissible spongiform encephalopathy (TSE) diseases are known to cross species barriers, but the pathologic and biochemical changes that occur during transmission are not well understood.To better understand these changes, we infected 6 hamster species with 263K hamster scrapie strain and, after each of 3 successive passages in the new species, analyzed abnormal proteinase K (PK)-resistant prion protein (PrPres) glycoform ratios, PrPres PK sensitivity, incubation periods, and lesion profiles.Furthermore, 2 polymorphic regions of the prion protein amino acid sequence correlated with profile differences in these TSE-infected hamster species.

View Article: PubMed Central - PubMed

Affiliation: National Institute of Allergy and Infectious Diseases, Hamilton, Montana, USA. kmeade-white@niaid.nih.gov

ABSTRACT
Transmissible spongiform encephalopathy (TSE) diseases are known to cross species barriers, but the pathologic and biochemical changes that occur during transmission are not well understood. To better understand these changes, we infected 6 hamster species with 263K hamster scrapie strain and, after each of 3 successive passages in the new species, analyzed abnormal proteinase K (PK)-resistant prion protein (PrPres) glycoform ratios, PrPres PK sensitivity, incubation periods, and lesion profiles. Unique 263K molecular and biochemical profiles evolved in each of the infected hamster species. Characteristics of 263K in the new hamster species seemed to correlate best with host factors rather than agent strain. Furthermore, 2 polymorphic regions of the prion protein amino acid sequence correlated with profile differences in these TSE-infected hamster species.

Show MeSH
Related in: MedlinePlus