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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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Immunohistochemical analysis of squirrel monkeys infected with chronic wasting disease (CWD) agent. Panels A, C, and E–M are from squirrel monkeys infected with CWD. Panels B and D are from an uninfected monkey showing no pathologic changes or positive staining for protease-resistant prion protein (PrPres). Panels A and B, cerebral cortex stained with hematoxylin and eosin; panels C and D, thalamus stained with antibody 3F4 against PrP (arrows); panels E and F, cerebellar granular cell layer and spinal cord, respectively, stained with antibody 3F4; panel G, gray matter within the internal capsule stained with antibody D13 against PrP; panel H, corpus callosum (right) stained with antibody D13 showing more intense staining than the adjacent cortex (left); panel I, frontal cortex (fc), claustrum (cl), and caudate (ca) stained with antibody 3F4 (abundant vacuoles in the putamen [arrows]); panels J–M, lymphatic tissue stained with antibody 3F4; panels J and K, PrPres staining in spleen of monkey 322; panels L and M, PrPres-positive mesenteric lymph node from orally infected monkey 301. Rectangles in panels J and L show areas enlarged in panels K and M, respectively. Antibodies D13 and 3F4 showed similar results for each monkey regarding the distribution, characteristics, and plaque size of PrPres. Scale bars: panels A–I, 50 μm; panel J, 100 μm; panels K and M, 25 μm; panel L, 250 μm.
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Figure 3: Immunohistochemical analysis of squirrel monkeys infected with chronic wasting disease (CWD) agent. Panels A, C, and E–M are from squirrel monkeys infected with CWD. Panels B and D are from an uninfected monkey showing no pathologic changes or positive staining for protease-resistant prion protein (PrPres). Panels A and B, cerebral cortex stained with hematoxylin and eosin; panels C and D, thalamus stained with antibody 3F4 against PrP (arrows); panels E and F, cerebellar granular cell layer and spinal cord, respectively, stained with antibody 3F4; panel G, gray matter within the internal capsule stained with antibody D13 against PrP; panel H, corpus callosum (right) stained with antibody D13 showing more intense staining than the adjacent cortex (left); panel I, frontal cortex (fc), claustrum (cl), and caudate (ca) stained with antibody 3F4 (abundant vacuoles in the putamen [arrows]); panels J–M, lymphatic tissue stained with antibody 3F4; panels J and K, PrPres staining in spleen of monkey 322; panels L and M, PrPres-positive mesenteric lymph node from orally infected monkey 301. Rectangles in panels J and L show areas enlarged in panels K and M, respectively. Antibodies D13 and 3F4 showed similar results for each monkey regarding the distribution, characteristics, and plaque size of PrPres. Scale bars: panels A–I, 50 μm; panel J, 100 μm; panels K and M, 25 μm; panel L, 250 μm.

Mentions: Tissues from squirrel monkeys euthanized after intracerebral injection with CWD (Table 1) were also examined by histopathologic analysis, including staining with hematoxylin and eosin and immunohistochemical detection of PrPres. All monkeys examined had spongiosis in the cerebral cortex, caudate, putamen, and thalamus (Figure 3, panel A). In addition, PrPres deposition was observed in many brain regions with large PrPres-positive plaques in the thalamus, cerebellum, and spinal cord (Figure 3, panels C, E, F) and in smaller plaques spread out in the gray matter of the internal capsule and white matter of the corpus callosum (Figure 3, panels G, H). The most abundant and consistent location for PrPres staining was found in the frontal cortex and in the fiber tracts of the claustrum (Figure 3, panel I). The adjacent caudate had severe spongiosis and astrocytosis but minimal PrPres (Figure 3, panel I). PrPres was also detected in lymph nodes and spleen, within follicles, in areas resembling follicular dendritic cells (Figure 3, panels K, M). Immunohistochemical analysis showed no PrPres in heart, kidney, adrenal gland, skeletal muscle, salivary gland, tongue, pancreas, white fat, and all regions of the gastrointestinal tract.


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)

Immunohistochemical analysis of squirrel monkeys infected with chronic wasting disease (CWD) agent. Panels A, C, and E–M are from squirrel monkeys infected with CWD. Panels B and D are from an uninfected monkey showing no pathologic changes or positive staining for protease-resistant prion protein (PrPres). Panels A and B, cerebral cortex stained with hematoxylin and eosin; panels C and D, thalamus stained with antibody 3F4 against PrP (arrows); panels E and F, cerebellar granular cell layer and spinal cord, respectively, stained with antibody 3F4; panel G, gray matter within the internal capsule stained with antibody D13 against PrP; panel H, corpus callosum (right) stained with antibody D13 showing more intense staining than the adjacent cortex (left); panel I, frontal cortex (fc), claustrum (cl), and caudate (ca) stained with antibody 3F4 (abundant vacuoles in the putamen [arrows]); panels J–M, lymphatic tissue stained with antibody 3F4; panels J and K, PrPres staining in spleen of monkey 322; panels L and M, PrPres-positive mesenteric lymph node from orally infected monkey 301. Rectangles in panels J and L show areas enlarged in panels K and M, respectively. Antibodies D13 and 3F4 showed similar results for each monkey regarding the distribution, characteristics, and plaque size of PrPres. Scale bars: panels A–I, 50 μm; panel J, 100 μm; panels K and M, 25 μm; panel L, 250 μm.
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Figure 3: Immunohistochemical analysis of squirrel monkeys infected with chronic wasting disease (CWD) agent. Panels A, C, and E–M are from squirrel monkeys infected with CWD. Panels B and D are from an uninfected monkey showing no pathologic changes or positive staining for protease-resistant prion protein (PrPres). Panels A and B, cerebral cortex stained with hematoxylin and eosin; panels C and D, thalamus stained with antibody 3F4 against PrP (arrows); panels E and F, cerebellar granular cell layer and spinal cord, respectively, stained with antibody 3F4; panel G, gray matter within the internal capsule stained with antibody D13 against PrP; panel H, corpus callosum (right) stained with antibody D13 showing more intense staining than the adjacent cortex (left); panel I, frontal cortex (fc), claustrum (cl), and caudate (ca) stained with antibody 3F4 (abundant vacuoles in the putamen [arrows]); panels J–M, lymphatic tissue stained with antibody 3F4; panels J and K, PrPres staining in spleen of monkey 322; panels L and M, PrPres-positive mesenteric lymph node from orally infected monkey 301. Rectangles in panels J and L show areas enlarged in panels K and M, respectively. Antibodies D13 and 3F4 showed similar results for each monkey regarding the distribution, characteristics, and plaque size of PrPres. Scale bars: panels A–I, 50 μm; panel J, 100 μm; panels K and M, 25 μm; panel L, 250 μm.
Mentions: Tissues from squirrel monkeys euthanized after intracerebral injection with CWD (Table 1) were also examined by histopathologic analysis, including staining with hematoxylin and eosin and immunohistochemical detection of PrPres. All monkeys examined had spongiosis in the cerebral cortex, caudate, putamen, and thalamus (Figure 3, panel A). In addition, PrPres deposition was observed in many brain regions with large PrPres-positive plaques in the thalamus, cerebellum, and spinal cord (Figure 3, panels C, E, F) and in smaller plaques spread out in the gray matter of the internal capsule and white matter of the corpus callosum (Figure 3, panels G, H). The most abundant and consistent location for PrPres staining was found in the frontal cortex and in the fiber tracts of the claustrum (Figure 3, panel I). The adjacent caudate had severe spongiosis and astrocytosis but minimal PrPres (Figure 3, panel I). PrPres was also detected in lymph nodes and spleen, within follicles, in areas resembling follicular dendritic cells (Figure 3, panels K, M). Immunohistochemical analysis showed no PrPres in heart, kidney, adrenal gland, skeletal muscle, salivary gland, tongue, pancreas, white fat, and all regions of the gastrointestinal tract.

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