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Susceptibilities of nonhuman primates to chronic wasting disease.

Race B, Meade-White KD, Miller MW, Barbian KD, Rubenstein R, LaFauci G, Cervenakova L, Favara C, Gardner D, Long D, Parnell M, Striebel J, Priola SA, Ward A, Williams ES, Race R, Chesebro B - Emerging Infect. Dis. (2009)

Bottom Line: Human susceptibility to CWD remains unproven despite likely exposure to CWD-infected cervids.In contrast, cynomolgus macaques have not shown evidence of clinical disease as of 70 months postinfection.Thus, these 2 species differed in susceptibility to CWD.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, Hamilton, Montana 59840, USA. raceb@niaid.nih.g

ABSTRACT
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy, or prion disease, that affects deer, elk, and moose. Human susceptibility to CWD remains unproven despite likely exposure to CWD-infected cervids. We used 2 nonhuman primate species, cynomolgus macaques and squirrel monkeys, as human models for CWD susceptibility. CWD was inoculated into these 2 species by intracerebral and oral routes. After intracerebral inoculation of squirrel monkeys, 7 of 8 CWD isolates induced a clinical wasting syndrome within 33-53 months. The monkeys' brains showed spongiform encephalopathy and protease-resistant prion protein (PrPres) diagnostic of prion disease. After oral exposure, 2 squirrel monkeys had PrPres in brain, spleen, and lymph nodes at 69 months postinfection. In contrast, cynomolgus macaques have not shown evidence of clinical disease as of 70 months postinfection. Thus, these 2 species differed in susceptibility to CWD. Because humans are evolutionarily closer to macaques than to squirrel monkeys, they may also be resistant to CWD.

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Related in: MedlinePlus

Comparison of prion protein sequences from various species. The following species are shown, and GenBank accession numbers are given when available: human (M13899), cynomolgus macaque (Cyno Mac) (U08298), squirrel monkey (Sq Mk) (genotype RML-A, see Table 4), squirrel monkey from Schneider et al. (31) (AY765385), squirrel monkey from Schätzl et al. (28) (U08310), mule deer (AY330343), and elk (AF156183). Numbering is based on the human sequence. Gray boxes indicate residues different from human residues. Alignment of the sequences was conducted with MegAlign software (DNAstar/Lasergene, Madison, WI, USA).
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Figure 4: Comparison of prion protein sequences from various species. The following species are shown, and GenBank accession numbers are given when available: human (M13899), cynomolgus macaque (Cyno Mac) (U08298), squirrel monkey (Sq Mk) (genotype RML-A, see Table 4), squirrel monkey from Schneider et al. (31) (AY765385), squirrel monkey from Schätzl et al. (28) (U08310), mule deer (AY330343), and elk (AF156183). Numbering is based on the human sequence. Gray boxes indicate residues different from human residues. Alignment of the sequences was conducted with MegAlign software (DNAstar/Lasergene, Madison, WI, USA).

Mentions: The PrP gene sequence can influence cross-species transmission of prion disease. Therefore, we compared squirrel monkey and cynomolgus macaque PrP gene sequences to look for differences that might account for different susceptibilities of these monkeys to CWD. In the PrP gene excluding the signal peptide, deer differed from squirrel monkeys at 17 residues and from cynomolgus macaques at 16 residues, but 14 of these differing residues were identical in squirrel monkeys and macaques (Figure 4). Therefore, there are only 2 residues in cynomolgus macaques (100 and 108) and 3 residues in squirrel monkeys (56, 159 and 182) at which these monkeys differ from deer and also from each other. These residues might play a role in susceptibility differences seen in our study.


Susceptibilities of nonhuman primates to chronic wasting disease.

Race B, Meade-White KD, Miller MW, Barbian KD, Rubenstein R, LaFauci G, Cervenakova L, Favara C, Gardner D, Long D, Parnell M, Striebel J, Priola SA, Ward A, Williams ES, Race R, Chesebro B - Emerging Infect. Dis. (2009)

Comparison of prion protein sequences from various species. The following species are shown, and GenBank accession numbers are given when available: human (M13899), cynomolgus macaque (Cyno Mac) (U08298), squirrel monkey (Sq Mk) (genotype RML-A, see Table 4), squirrel monkey from Schneider et al. (31) (AY765385), squirrel monkey from Schätzl et al. (28) (U08310), mule deer (AY330343), and elk (AF156183). Numbering is based on the human sequence. Gray boxes indicate residues different from human residues. Alignment of the sequences was conducted with MegAlign software (DNAstar/Lasergene, Madison, WI, USA).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2819871&req=5

Figure 4: Comparison of prion protein sequences from various species. The following species are shown, and GenBank accession numbers are given when available: human (M13899), cynomolgus macaque (Cyno Mac) (U08298), squirrel monkey (Sq Mk) (genotype RML-A, see Table 4), squirrel monkey from Schneider et al. (31) (AY765385), squirrel monkey from Schätzl et al. (28) (U08310), mule deer (AY330343), and elk (AF156183). Numbering is based on the human sequence. Gray boxes indicate residues different from human residues. Alignment of the sequences was conducted with MegAlign software (DNAstar/Lasergene, Madison, WI, USA).
Mentions: The PrP gene sequence can influence cross-species transmission of prion disease. Therefore, we compared squirrel monkey and cynomolgus macaque PrP gene sequences to look for differences that might account for different susceptibilities of these monkeys to CWD. In the PrP gene excluding the signal peptide, deer differed from squirrel monkeys at 17 residues and from cynomolgus macaques at 16 residues, but 14 of these differing residues were identical in squirrel monkeys and macaques (Figure 4). Therefore, there are only 2 residues in cynomolgus macaques (100 and 108) and 3 residues in squirrel monkeys (56, 159 and 182) at which these monkeys differ from deer and also from each other. These residues might play a role in susceptibility differences seen in our study.

Bottom Line: Human susceptibility to CWD remains unproven despite likely exposure to CWD-infected cervids.In contrast, cynomolgus macaques have not shown evidence of clinical disease as of 70 months postinfection.Thus, these 2 species differed in susceptibility to CWD.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, Hamilton, Montana 59840, USA. raceb@niaid.nih.g

ABSTRACT
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy, or prion disease, that affects deer, elk, and moose. Human susceptibility to CWD remains unproven despite likely exposure to CWD-infected cervids. We used 2 nonhuman primate species, cynomolgus macaques and squirrel monkeys, as human models for CWD susceptibility. CWD was inoculated into these 2 species by intracerebral and oral routes. After intracerebral inoculation of squirrel monkeys, 7 of 8 CWD isolates induced a clinical wasting syndrome within 33-53 months. The monkeys' brains showed spongiform encephalopathy and protease-resistant prion protein (PrPres) diagnostic of prion disease. After oral exposure, 2 squirrel monkeys had PrPres in brain, spleen, and lymph nodes at 69 months postinfection. In contrast, cynomolgus macaques have not shown evidence of clinical disease as of 70 months postinfection. Thus, these 2 species differed in susceptibility to CWD. Because humans are evolutionarily closer to macaques than to squirrel monkeys, they may also be resistant to CWD.

Show MeSH
Related in: MedlinePlus