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Chronic wasting disease agents in nonhuman primates.

Race B, Meade-White KD, Phillips K, Striebel J, Race R, Chesebro B - Emerging Infect. Dis. (2014)

Bottom Line: Assessment of its zoonotic potential is critical.To evaluate primate susceptibility, we tested monkeys from 2 genera.We found that 100% of intracerebrally inoculated and 92% of orally inoculated squirrel monkeys were susceptible, but cynomolgus macaques were not, suggesting possible low risk for humans.

View Article: PubMed Central - PubMed

ABSTRACT
Chronic wasting disease is a prion disease of cervids. Assessment of its zoonotic potential is critical. To evaluate primate susceptibility, we tested monkeys from 2 genera. We found that 100% of intracerebrally inoculated and 92% of orally inoculated squirrel monkeys were susceptible, but cynomolgus macaques were not, suggesting possible low risk for humans.

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Neuropathologic features and immunoblot results of second-passage squirrel monkeys that had chronic wasting disease (CWD). Scale bar represents 50 µM and is applicable to panels A and B. Panels A and B show neuropathologic changes in the occipital lobe of SMP2-CWD monkey 977, which was euthanized at 24 months postinoculation. A) Hematoxylin and eosin staining show prominent spongiform changes. B) Immunohistochemical staining for disease-associated prion protein (PrPres) (brown) with anti-PrP antibody D13. C) Results of Western blot for PrPres in brain tissue of cervids and its respective first and second passage in squirrel monkeys. MD-1 was used to infect SM308, and SM308 was used to infect SM977. Lanes 1, 2, 5, and 6, 0.6 mg brain equivalents. Lanes 3 and 7, 0.36 mg brain equivalents to give similar signal intensities to the other samples. Lane 4, blank (Bl). Apparent molecular weights (in kDa) are provided on the left side of panel C. Immunoblot was probed with anti-PrP antibody L42. When comparing the 2 central bands, cervid CWD had a more intense band at 25.5 kDa; SM-CWD (nos. 308 and 322) and SM2-CWD (nos. 977 and 840) were more intense at 27 kDa.
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Figure 2: Neuropathologic features and immunoblot results of second-passage squirrel monkeys that had chronic wasting disease (CWD). Scale bar represents 50 µM and is applicable to panels A and B. Panels A and B show neuropathologic changes in the occipital lobe of SMP2-CWD monkey 977, which was euthanized at 24 months postinoculation. A) Hematoxylin and eosin staining show prominent spongiform changes. B) Immunohistochemical staining for disease-associated prion protein (PrPres) (brown) with anti-PrP antibody D13. C) Results of Western blot for PrPres in brain tissue of cervids and its respective first and second passage in squirrel monkeys. MD-1 was used to infect SM308, and SM308 was used to infect SM977. Lanes 1, 2, 5, and 6, 0.6 mg brain equivalents. Lanes 3 and 7, 0.36 mg brain equivalents to give similar signal intensities to the other samples. Lane 4, blank (Bl). Apparent molecular weights (in kDa) are provided on the left side of panel C. Immunoblot was probed with anti-PrP antibody L42. When comparing the 2 central bands, cervid CWD had a more intense band at 25.5 kDa; SM-CWD (nos. 308 and 322) and SM2-CWD (nos. 977 and 840) were more intense at 27 kDa.

Mentions: Two SM-CWD brain samples were inoculated into squirrel monkeys and cynomolgus macaques to verify that SM-CWD was infectious, test for further adaptation, and to see if SM-CWD was infectious to a broader range of nonhuman primates. Two squirrel monkeys inoculated intracerebrally with SM-CWD brain homogenates (SMP2-CWD) were euthanized at 23–24 mpi (Table 1). These incubation periods decreased by >11 months compared with that of the donor squirrel monkey. Neurologic signs in the 2 SMP2-CWD were more pronounced than observed during the first passage; however, weight loss was reduced. Neuropathologic examination and Western blot for PrPres confirmed TSE in both squirrel monkeys. In contrast to SM-CWD infections, the SMP2-CWD-infected brains had spongiform lesions and PrPres deposition in the occipital lobe (Figure 2, panels A, B). Biochemical comparison of glycoform patterns among CWD, SM-CWD, and SMP2-CWD were made by using 3 different anti-PrP antibodies (L42, 6H4, and 3F4) (Technical Appendix). In all cases, SM2-CWD had a greater proportion of unglycosylated PrPres and a lower proportion of double glycosylated PrPres than did SM-CWD (Figure 2, panel C). The decreased time of manifestation of disease, differences in glycoform patterns, and distribution of PrPres in brain tissue suggested that the CWD agent was still adapting within the squirrel monkey. However, similar to CWD, SM-CWD had not caused prion disease in cynomolgus macaques by 72 mpi (Table 2).


Chronic wasting disease agents in nonhuman primates.

Race B, Meade-White KD, Phillips K, Striebel J, Race R, Chesebro B - Emerging Infect. Dis. (2014)

Neuropathologic features and immunoblot results of second-passage squirrel monkeys that had chronic wasting disease (CWD). Scale bar represents 50 µM and is applicable to panels A and B. Panels A and B show neuropathologic changes in the occipital lobe of SMP2-CWD monkey 977, which was euthanized at 24 months postinoculation. A) Hematoxylin and eosin staining show prominent spongiform changes. B) Immunohistochemical staining for disease-associated prion protein (PrPres) (brown) with anti-PrP antibody D13. C) Results of Western blot for PrPres in brain tissue of cervids and its respective first and second passage in squirrel monkeys. MD-1 was used to infect SM308, and SM308 was used to infect SM977. Lanes 1, 2, 5, and 6, 0.6 mg brain equivalents. Lanes 3 and 7, 0.36 mg brain equivalents to give similar signal intensities to the other samples. Lane 4, blank (Bl). Apparent molecular weights (in kDa) are provided on the left side of panel C. Immunoblot was probed with anti-PrP antibody L42. When comparing the 2 central bands, cervid CWD had a more intense band at 25.5 kDa; SM-CWD (nos. 308 and 322) and SM2-CWD (nos. 977 and 840) were more intense at 27 kDa.
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Related In: Results  -  Collection

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Figure 2: Neuropathologic features and immunoblot results of second-passage squirrel monkeys that had chronic wasting disease (CWD). Scale bar represents 50 µM and is applicable to panels A and B. Panels A and B show neuropathologic changes in the occipital lobe of SMP2-CWD monkey 977, which was euthanized at 24 months postinoculation. A) Hematoxylin and eosin staining show prominent spongiform changes. B) Immunohistochemical staining for disease-associated prion protein (PrPres) (brown) with anti-PrP antibody D13. C) Results of Western blot for PrPres in brain tissue of cervids and its respective first and second passage in squirrel monkeys. MD-1 was used to infect SM308, and SM308 was used to infect SM977. Lanes 1, 2, 5, and 6, 0.6 mg brain equivalents. Lanes 3 and 7, 0.36 mg brain equivalents to give similar signal intensities to the other samples. Lane 4, blank (Bl). Apparent molecular weights (in kDa) are provided on the left side of panel C. Immunoblot was probed with anti-PrP antibody L42. When comparing the 2 central bands, cervid CWD had a more intense band at 25.5 kDa; SM-CWD (nos. 308 and 322) and SM2-CWD (nos. 977 and 840) were more intense at 27 kDa.
Mentions: Two SM-CWD brain samples were inoculated into squirrel monkeys and cynomolgus macaques to verify that SM-CWD was infectious, test for further adaptation, and to see if SM-CWD was infectious to a broader range of nonhuman primates. Two squirrel monkeys inoculated intracerebrally with SM-CWD brain homogenates (SMP2-CWD) were euthanized at 23–24 mpi (Table 1). These incubation periods decreased by >11 months compared with that of the donor squirrel monkey. Neurologic signs in the 2 SMP2-CWD were more pronounced than observed during the first passage; however, weight loss was reduced. Neuropathologic examination and Western blot for PrPres confirmed TSE in both squirrel monkeys. In contrast to SM-CWD infections, the SMP2-CWD-infected brains had spongiform lesions and PrPres deposition in the occipital lobe (Figure 2, panels A, B). Biochemical comparison of glycoform patterns among CWD, SM-CWD, and SMP2-CWD were made by using 3 different anti-PrP antibodies (L42, 6H4, and 3F4) (Technical Appendix). In all cases, SM2-CWD had a greater proportion of unglycosylated PrPres and a lower proportion of double glycosylated PrPres than did SM-CWD (Figure 2, panel C). The decreased time of manifestation of disease, differences in glycoform patterns, and distribution of PrPres in brain tissue suggested that the CWD agent was still adapting within the squirrel monkey. However, similar to CWD, SM-CWD had not caused prion disease in cynomolgus macaques by 72 mpi (Table 2).

Bottom Line: Assessment of its zoonotic potential is critical.To evaluate primate susceptibility, we tested monkeys from 2 genera.We found that 100% of intracerebrally inoculated and 92% of orally inoculated squirrel monkeys were susceptible, but cynomolgus macaques were not, suggesting possible low risk for humans.

View Article: PubMed Central - PubMed

ABSTRACT
Chronic wasting disease is a prion disease of cervids. Assessment of its zoonotic potential is critical. To evaluate primate susceptibility, we tested monkeys from 2 genera. We found that 100% of intracerebrally inoculated and 92% of orally inoculated squirrel monkeys were susceptible, but cynomolgus macaques were not, suggesting possible low risk for humans.

Show MeSH
Related in: MedlinePlus