Limits...
Detection of CWD prions in urine and saliva of deer by transgenic mouse bioassay.

Haley NJ, Seelig DM, Zabel MD, Telling GC, Hoover EA - PLoS ONE (2009)

Bottom Line: The mechanisms of CWD transmission are poorly understood, though bodily fluids are thought to play an important role.In addition, PrP(CWD) was detected in pooled and concentrated urine by protein misfolding cyclic amplification (PMCA).These findings help extend our understanding of CWD prion shedding and transmission and portend the detection of infectious prions in body fluids in other prion infections.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.

ABSTRACT
Chronic wasting disease (CWD) is a prion disease affecting captive and free-ranging cervids (e.g. deer, elk, and moose). The mechanisms of CWD transmission are poorly understood, though bodily fluids are thought to play an important role. Here we report the presence of infectious prions in the urine and saliva of deer with chronic wasting disease (CWD). Prion infectivity was detected by bioassay of concentrated, dialyzed urine and saliva in transgenic mice expressing the cervid PrP gene (Tg[CerPrP] mice). In addition, PrP(CWD) was detected in pooled and concentrated urine by protein misfolding cyclic amplification (PMCA). The concentration of abnormal prion protein in bodily fluids was very low, as indicated by: undetectable PrP(CWD) levels by traditional assays (western blot, ELISA) and prolonged incubation periods and incomplete TSE attack rates in inoculated Tg(CerPrP) mice (373(+/-)3 days in 2 of 9 urine-inoculated mice and 342(+/-)109 days in 8 of 9 saliva-inoculated mice). These findings help extend our understanding of CWD prion shedding and transmission and portend the detection of infectious prions in body fluids in other prion infections.

Show MeSH

Related in: MedlinePlus

Histopathologic evaluation of renal tissues from donor cervids.(A) Minimal, chronic and proliferative glomerular disease and (B) mild interstitial fibrosis and lymphocytic infiltration were observed in 4 out of 5 donor deer. The remaining deer showed evidence of mild lymphocytic glomerulonephritis (C) as well as “tubular proteinosis.” (D, arrows).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2654070&req=5

pone-0004848-g003: Histopathologic evaluation of renal tissues from donor cervids.(A) Minimal, chronic and proliferative glomerular disease and (B) mild interstitial fibrosis and lymphocytic infiltration were observed in 4 out of 5 donor deer. The remaining deer showed evidence of mild lymphocytic glomerulonephritis (C) as well as “tubular proteinosis.” (D, arrows).

Mentions: To identify potential pathological mechanisms for prionuria, histopathologic examination of donor renal tissues was also performed. Microscopic evaluation of H&E stained kidney sections from each of the donor deer revealed minimal histologic disease in 4 of the 5 animals. Lesions in these animals were characterized by the combination of minimal proliferative glomerular disease and mild interstitial fibrosis and lymphocytic inflammation (Figure 3A and B). In these animals, there was no appreciable histologic evidence of proteinuria or pyelonephritis. In the fifth animal, more significant renal pathology was detected. In this animal, there was a combination of mild, chronic, lymphocytic glomerulonephritis, which was similar to the previous 4 animals, and a moderately severe, chronic, lymphocytic interstitial nephritis with light microscopic evidence of renal protein loss (“tubular proteinosis”). (Figures 3C and D).


Detection of CWD prions in urine and saliva of deer by transgenic mouse bioassay.

Haley NJ, Seelig DM, Zabel MD, Telling GC, Hoover EA - PLoS ONE (2009)

Histopathologic evaluation of renal tissues from donor cervids.(A) Minimal, chronic and proliferative glomerular disease and (B) mild interstitial fibrosis and lymphocytic infiltration were observed in 4 out of 5 donor deer. The remaining deer showed evidence of mild lymphocytic glomerulonephritis (C) as well as “tubular proteinosis.” (D, arrows).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2654070&req=5

pone-0004848-g003: Histopathologic evaluation of renal tissues from donor cervids.(A) Minimal, chronic and proliferative glomerular disease and (B) mild interstitial fibrosis and lymphocytic infiltration were observed in 4 out of 5 donor deer. The remaining deer showed evidence of mild lymphocytic glomerulonephritis (C) as well as “tubular proteinosis.” (D, arrows).
Mentions: To identify potential pathological mechanisms for prionuria, histopathologic examination of donor renal tissues was also performed. Microscopic evaluation of H&E stained kidney sections from each of the donor deer revealed minimal histologic disease in 4 of the 5 animals. Lesions in these animals were characterized by the combination of minimal proliferative glomerular disease and mild interstitial fibrosis and lymphocytic inflammation (Figure 3A and B). In these animals, there was no appreciable histologic evidence of proteinuria or pyelonephritis. In the fifth animal, more significant renal pathology was detected. In this animal, there was a combination of mild, chronic, lymphocytic glomerulonephritis, which was similar to the previous 4 animals, and a moderately severe, chronic, lymphocytic interstitial nephritis with light microscopic evidence of renal protein loss (“tubular proteinosis”). (Figures 3C and D).

Bottom Line: The mechanisms of CWD transmission are poorly understood, though bodily fluids are thought to play an important role.In addition, PrP(CWD) was detected in pooled and concentrated urine by protein misfolding cyclic amplification (PMCA).These findings help extend our understanding of CWD prion shedding and transmission and portend the detection of infectious prions in body fluids in other prion infections.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.

ABSTRACT
Chronic wasting disease (CWD) is a prion disease affecting captive and free-ranging cervids (e.g. deer, elk, and moose). The mechanisms of CWD transmission are poorly understood, though bodily fluids are thought to play an important role. Here we report the presence of infectious prions in the urine and saliva of deer with chronic wasting disease (CWD). Prion infectivity was detected by bioassay of concentrated, dialyzed urine and saliva in transgenic mice expressing the cervid PrP gene (Tg[CerPrP] mice). In addition, PrP(CWD) was detected in pooled and concentrated urine by protein misfolding cyclic amplification (PMCA). The concentration of abnormal prion protein in bodily fluids was very low, as indicated by: undetectable PrP(CWD) levels by traditional assays (western blot, ELISA) and prolonged incubation periods and incomplete TSE attack rates in inoculated Tg(CerPrP) mice (373(+/-)3 days in 2 of 9 urine-inoculated mice and 342(+/-)109 days in 8 of 9 saliva-inoculated mice). These findings help extend our understanding of CWD prion shedding and transmission and portend the detection of infectious prions in body fluids in other prion infections.

Show MeSH
Related in: MedlinePlus