ライフサイエンスコーパス: CWD

1 CWD clams had considerably higher (by ~8-12 degrees C) l

2 CWD epidemics are occurring in free-ranging cervids at s

3 CWD properties were faithfully maintained in deer follow

4 ical parameters of 24 CWD IRIS patients, 189 CWD patients without IRIS, and 89 healthy individuals.

5 s of IRIS and immunological parameters of 24 CWD IRIS patients, 189 CWD patients without IRIS, and 89

6 fluminea from two pristine populations and a CWD population.

7 Feline-adapted CWD (Fel(CWD)) was demonstrated in the brains of all of

8 define PrP sequence determinants that affect CWD transmission to humans.

9 5 and 96 in the unstructured region affected CWD propagation, their protective effects were overridde

10 ed prion shedding as early as 3 months after CWD exposure and sustained shedding throughout the disea

11 lymorphisms that provided protection against CWD had distinct and varied influences.

12 Although CWD transmissions indicated stable, independent strain p

13 PMCA results from hamster and CWD agent-infected elk prions yielded similar findings.

14 converted bovine than feline rPrP; (iv) and CWD, fCWD, BSE, and FSE all converted human rPrP, althou

15 he transmission of infectious pathogens, and CWD in particular.

16 Here we show that asymptomatic CWD-infected mule deer (Odocoileus hemionus) excrete CWD

17 y rates increased independently with average CWD and with basal area, and they increased disproportio

18 an model to examine the relationship between CWD prevalence and PRNP 132L allele frequency.

19 re more likely to be converted to amyloid by CWD prions than were their truncated forms.

20 of the molecule to facilitate conversion by CWD prions.

21 can be converted into the misfolded form by CWD PrP(Sc), we performed experiments using the protein

22 Whether noncervid species can be infected by CWD and thereby serve as reservoirs for the infection is

23 o elucidate that centripetal and centrifugal CWD prion transit pathways involve cells and fibers of t

24 mission to SGH, the incubation period of CKY CWD was approximately 150 days longer than WST CWD.

25 D21/35 expression completely resist clinical CWD upon peripheral infection.

26 may be insensitive to early or sub-clinical CWD that are important to understanding CWD transmission

27 wing clinical signs of infection (clinically CWD-infected) and in some placentomes from pre-clinicall

28 and in some placentomes from pre-clinically CWD-infected dams.

29 n and hydrolysis in a cocktail of commercial CWD enzymes produced >90% theoretical glucose and >63% t

30 ions were taken as the control weather data (CWD).

31 PrP were highly susceptible to elk and deer CWD prions but were concurrently less susceptible to hum

32 t prairie voles are susceptible to mule deer CWD prions in vivo and that sPMCA amplification of CWD p

33 35-year mean annual climatic water deficit (CWD)] and competition (i.e. tree basal area) on tree mor

34 Expressing cell wall-degrading (CWD) enzymes (e.g. xylanases) in plant feedstocks could

35 rodents and suggest that the cervid-derived CWD inocula may have contained or diverged into at least

36 We used the cooling water discharge (CWD) area of a power plant as a model for long-term warm

37 bial treatment of classic Whipple's disease (CWD), the chronic systemic infection with Tropheryma whi

38 dams infected with chronic wasting disease (CWD) (1).

39 -QuIC) and compared chronic wasting disease (CWD) and classical bovine spongiform encephalopathy (cBS

40 n to be affected by chronic wasting disease (CWD) and from 210 free-ranging white-tailed deer harvest

41 r prions that cause chronic wasting disease (CWD) and influences the risk of transmission to suscepti

42 to determine (i) if chronic wasting disease (CWD) blood infectivity is associated with the cellular v

43 Chronic wasting disease (CWD) in cervids and bovine spongiform encephalopathy (BS

44 In chronic wasting disease (CWD) in cervids and in scrapie in sheep, prions appear t

45 signature trait of chronic wasting disease (CWD) in cervids.

46 The emergence of chronic wasting disease (CWD) in deer and elk in an increasingly wide geographic

47 otypic diversity of chronic wasting disease (CWD) in different host species that express the same pri

48 Chronic wasting disease (CWD) is a fatal prion disease in deer and elk.

49 Chronic wasting disease (CWD) is a fatal prion disease of North American deer and

50 Chronic wasting disease (CWD) is a fatal spongiform encephalopathy that is effici

51 Chronic wasting disease (CWD) is a fatal, endemic prion disease of wild and capti

52 Chronic wasting disease (CWD) is a highly contagious always fatal neurodegenerati

53 Chronic wasting disease (CWD) is a naturally occurring, fatal neurodegenerative d

54 Chronic wasting disease (CWD) is a neurodegenerative prion disease of cervids.

55 Chronic wasting disease (CWD) is a prion disease of cervids that causes neurodege

56 Chronic wasting disease (CWD) is a prion disorder of increasing prevalence within

57 Chronic wasting disease (CWD) is a rapidly spreading prion disorder affecting cap

58 Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE)

59 invasion.IMPORTANCE Chronic wasting disease (CWD) is a universally fatal transmissible spongiform enc

60 Chronic wasting disease (CWD) is an emergent, rapidly spreading prion disease of

61 Chronic wasting disease (CWD) is an emerging and uniformly fatal prion disease af

62 Chronic wasting disease (CWD) is an emerging prion disease of captive and free-ra

63 the transmission of chronic wasting disease (CWD) of cervids and allow prion strain discrimination.

64 Chronic wasting disease (CWD) of cervids is associated with conversion of the nor

65 diseases, including chronic wasting disease (CWD) of cervids, is the potential presence of prions in

66 seases that include chronic wasting disease (CWD) of cervids.

67 crapie of sheep and chronic wasting disease (CWD) of several species in the deer family-are transmitt

68 tious diseases such chronic wasting disease (CWD) or bovine tuberculosis.

69 While chronic wasting disease (CWD) prion transmission, entry, and trafficking remain i

70 s are infected with chronic wasting disease (CWD) prions by oral and nasal mucosal exposure, and stud

71 est deer saliva for chronic wasting disease (CWD) prions.

72 nostic detection of chronic wasting disease (CWD) relies on immunodetection of misfolded CWD prion pr

73 ile transmission of chronic wasting disease (CWD) remains incompletely elucidated, studies in rodents

74 sion of scrapie and chronic wasting disease (CWD) via the environment.

75 of strains causing chronic wasting disease (CWD), a burgeoning prion epidemic of cervids, is unknown

76 ally susceptible to chronic wasting disease (CWD), a burgeoning, contagious epidemic of uncertain ori

77 been infected with chronic wasting disease (CWD), a contagious, fatal prion disease, and compared al

78 n of prions causing chronic wasting disease (CWD), a fatal, transmissible, neurodegenerative disorder

79 Chronic wasting disease (CWD), a prion disease affecting free-ranging and captive

80 Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervi

81 Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervi

82 Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of deer,

83 Chronic wasting disease (CWD), the only known prion disease endemic in wildlife,

84 d susceptibility to chronic wasting disease (CWD), the prion disease of cervids.

85 n areas affected by chronic wasting disease (CWD), we evaluated the susceptibility of the domestic ca

86 lipid content from chronic wasting disease (CWD)-infected white-tailed deer brain homogenates and fo

87 deer with clinical chronic wasting disease (CWD).

88 y be susceptible to chronic wasting disease (CWD).

89 prions that caused chronic wasting disease (CWD; hereafter "CWD prions") in deer, using 2 isolates f

90 Typical of prion diseases, CWD is characterized by the conversion of the native pro

91 Typical of prion diseases, CWD is characterized by the conversion of the native, pr

92 on and pathways of prion spread during early CWD infection remain unknown.

93 To investigate this knowledge gap in early CWD pathogenesis, we exposed white-tailed deer to CWD pr

94 nasal mucosal exposure, and studies of early CWD pathogenesis have implicated pharyngeal lymphoid tis

95 cted mule deer (Odocoileus hemionus) excrete CWD prions in their faeces long before they develop clin

96 A major hypothesis to explain CWD's florid spread is that prions are shed in excreta a

97 olymorphism at codon 132 can markedly extend CWD latency when the minor leucine allele (132L) is pres

98 r lingual abrasions substantially facilitate CWD transmission, revealing a cofactor that may be signi

99 Feline-adapted CWD (Fel(CWD)) was demonstrated in the brains of all of the affec

100 ns consistent with the early stage of feline CWD.

101 smission to a new species, we studied feline CWD (fCWD) and feline BSE (i.e., feline spongiform encep

102 Upon subpassage, feline CWD was transmitted to all i.c.-inoculated cats with a d

103 icroenvironment, revealing a source of fetal CWD exposure prior to the birthing process, maternal gro

104 itivity of blood-based diagnostic assays for CWD and other TSEs.

105 stitute a substantial structural barrier for CWD transmission to humans and helps illuminate the mole

106 t final inoculation and tissues examined for CWD-associated prion proteins by immunohistochemistry.

107 ide the first landscape predictive model for CWD based solely on soil characteristics.

108 automated testing of antemortem samples for CWD.

109 large-scale and rapid automated testing for CWD diagnosis.

110 er to saliva, blood, or urine and feces from CWD-positive deer.

111 ith the blood mononuclear cell fraction from CWD(+) donor deer became PrP(CWD) positive by 19 months

112 ve tract and in fetal tissues harvested from CWD experimentally and naturally exposed cervids (1, 2).

113 d but not in allantoic fluids harvested from CWD-infected Reeves' muntjac dams showing clinical signs

114 that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.

115 tinal tissues along with blood and obex from CWD-exposed cervids (comprising 27 animals and >350 indi

116 three of four deer receiving platelets from CWD(+) donor deer became PrP(CWD) positive in as little

117 The results for inocula prepared from CWD-positive deer with or without CWD-resistant genotype

118 ally collected saliva and urine samples from CWD-exposed white-tailed deer.

119 Brain samples from CWD-positive elk, white-tailed deer, and mule deer produ

120 Here, CWD agent obtained from a deer expressing the 96SS genot

121 sed chronic wasting disease (CWD; hereafter "CWD prions") in deer, using 2 isolates for each disease.

122 e-tailed deer in Wisconsin's area of highest CWD prevalence.

123 he field from areas with current or historic CWD endemicity.

124 These results are pertinent to horizontal CWD transmission in wild cervids.

125 n protein (PrP) that prevent or permit human CWD infection are unknown, NMR-based structural studies

126 To test this hypothesis, CWD-positive brain homogenate was mixed with montmorillo

127 These studies revealed the following: (i) CWD and BSE seeded their homologous species' PrP best; (

128 Moreover, we identified CWD PrP(RES) associated with the cell bodies and process

129 that RT-QuIC is useful for both identifying CWD-infected animals and facilitating epidemiological st

130 tified two additional residues that impacted CWD conversion of human PrP.

131 carriers capable of significantly impacting CWD ecology.

132 rine is thought to be an important factor in CWD transmission.

133 le, sandy loam soil (SLS) typically found in CWD endemic areas in Colorado; and purified montmorillon

134 The findings that IRIS in CWD mainly are mediated by nonspecific activation of CD4

135 instrumental in the pathogenesis of IRIS in CWD.

136 e immunological processes underlying IRIS in CWD.

137 peripheral and central autonomic networks in CWD neuroinvasion and neuropathogenesis and suggest that

138 titution on treatment was more pronounced in CWD patients with IRIS than in those without IRIS.

139 owed that the PK cleavage site of PrP(Sc) in CWD occurred at residues 82 and 78, similar to that of P

140 ubiquitinated proteins during heat stress in CWD clams.

141 whether the increase in thermal tolerance in CWD clams are due to genetic adaptation and/or phenotypi

142 usceptibility to prion infections, including CWD, can be dependent on the amino acid sequence of the

143 n scrapie-infected sheep but not in infected CWD-infected deer.

144 t the level of protein-protein interactions, CWD adapts to a new species more readily than does BSE a

145 t represents a viable vehicle for intranasal CWD prion exposure.

146 (CWD) relies on immunodetection of misfolded CWD prion protein (PrP(CWD)) by western blotting, ELISA,

147 shown to be effective surrogates of natural CWD, uncertainties remain regarding the mechanisms by wh

148 for swine to serve as hosts for the agent of CWD is unknown.

149 ions in vivo and that sPMCA amplification of CWD prions in vole brain enhances the infectivity of CWD

150 pigs can support low-level amplification of CWD prions, although the species barrier to CWD infectio

151 n attempt to elucidate this unique aspect of CWD pathogenesis.

152 differences between the species barriers of CWD and BSE.

153 To facilitate studies of the biology of CWD prions, we generated five lines of transgenic (Tg) m

154 s this issue directly, we exposed cohorts of CWD-naive deer to saliva, blood, or urine and feces from

155 nvolved in the epidemiological complexity of CWD infection in natural populations of white-tailed dee

156 ndings have impact on our current concept of CWD disease transmission.

157 of prion infectious doses over the course of CWD infection.

158 ipid extraction enabled RT-QuIC detection of CWD prions in a 2-log10-greater concentration of brain s

159 MCA) assay for highly efficient detection of CWD prions in blood samples.

160 relatively sensitive assay for detection of CWD prions in RAMALT biopsy specimens and, with further

161 mplification (sPMCA) to improve detection of CWD prior to the onset of clinical signs.

162 issue of choice for use for the diagnosis of CWD in white-tailed deer, the results of the present stu

163 d test for routine, live animal diagnosis of CWD.

164 vitro assay to show that infectious doses of CWD prions are in fact shed throughout the multiyear dis

165 lood CD14(+) monocytes developed evidence of CWD infection (immunohistochemistry and Western blot ana

166 of PrP(CWD) in the body fluids or excreta of CWD-susceptible species.

167 foodstuff tainted with prions from feces of CWD-infected cervids and scrapie-infected sheep.

168 rface that sustains the developing fetus, of CWD-infected dams.

169 Identification of CWD-affected animals currently requires postmortem analy

170 ns in vole brain enhances the infectivity of CWD for this species.

171 fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion inf

172 Localization of CWD infectivity with leukocyte subpopulations may aid in

173 tibility and to develop new rodent models of CWD.

174 of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming o

175 For serial passages of CWD isolates in Syrian golden hamsters, incubation perio

176 ion of cervid PrP(C) and the pathogenesis of CWD infection in transgenic mice expressing the normal c

177 rodent species, the apparent persistence of CWD prions in the environment, and the inevitable exposu

178 These data highlight the two phases of CWD infection: a robust prion amplification in systemic

179 The zoonotic potential of CWD is unknown, as well as the mechanism for its highly

180 sed concerns about the zoonotic potential of CWD.

181 he probability of the persistent presence of CWD in a region of northern Illinois using CWD surveilla

182 haracteristics of the persistent presence of CWD.

183 in Wisconsin where the overall prevalence of CWD among the deer was approximately 4 to 6%.

184 racteristics may increase the probability of CWD transmission via environmental contamination.

185 the infectivity and adapt the host range of CWD prions and thereby may be useful to assess determina

186 lly exposed pigs could act as a reservoir of CWD infectivity.IMPORTANCE We challenged domestic swine

187 These results indicate the first site of CWD prion entry is in the oropharynx, and the initial ph

188 sults demonstrate that transspecies sPMCA of CWD prions can enhance the infectivity and adapt the hos

189 The CKY strain of CWD had a shorter incubation period than the WST strain

190 ter incubation period than the WST strain of CWD, but after transmission to SGH, the incubation perio

191 ssue and thus may prove useful in studies of CWD pathogenesis and transmission by oral or other natur

192 l cells within the enteric nervous system of CWD-infected Tg(CerPrP-E) mice.

193 High thermal tolerance of CWD clams was associated with overexpression of heat sho

194 s help to explain the facile transmission of CWD among cervids and prompt caution concerning contact

195 een suggested as the mode of transmission of CWD and scrapie among herbivores susceptible to these pr

196 ion of prions may facilitate transmission of CWD and, perhaps, other prion infections.

197 on, we documented horizontal transmission of CWD from inoculated mice and to un-inoculated cohabitant

198 fer unique insights into the transmission of CWD in particular and prion infection and trafficking ov

199 y, pathogenesis, and lateral transmission of CWD infection in Tg[CerPrP] mice, affirming this model a

200 Here, we demonstrate aerosol transmission of CWD to deer with a prion dose >20-fold lower than that u

201 Although the transmission of CWD to humans has not been proven, it remains a possibil

202 Determining the risk of transmission of CWD to humans is of utmost importance, considering that

203 (ii) the barrier preventing transmission of CWD to humans may be less robust than estimated.

204 This is the first reported transmission of CWD to primates.

205 nce and efficient horizontal transmission of CWD within deer herds, as well as prion transmission amo

206 ent between simulations of Yp or Yw based on CWD and those based on GWD was poor with the latter havi

207 of naturally occurring PrP polymorphisms on CWD susceptibility were accurately reproduced in Tg mice

208 eas those inoculated orally with deer-origin CWD prions did not.

209 transgenic mice, we identified two prevalent CWD strains with divergent biological properties but com

210 PrP(CWD)-generating activity was detected in a range of tiss

211 blotting (WB) indicated that PrP(263K), PrP(CWD), and PrP(BSE) were reduced by at least 2 log10, 1-2

212 Although PrP(CWD) was not detected by either method in the initial da

213 g cyclic amplification (PMCA) to amplify PrP(CWD) in vitro.

214 st enhanced degradation of PrP(263K) and PrP(CWD).

215 nd performed serial necropsies to assess PrP(CWD) tissue distribution by real-time quaking-induced co

216 l fraction from CWD(+) donor deer became PrP(CWD) positive by 19 months postinoculation, whereas none

217 platelets from CWD(+) donor deer became PrP(CWD) positive in as little as 6 months postinoculation,

218 Terminal disease is characterized by PrP(CWD) accumulation in the brain and lymphoid tissues of a

219 P(C), to a protease-resistant conformer, PrP(CWD).

220 apie (PrP(263K)), chronic waste disease (PrP(CWD)), and bovine spongiform encephalopathy (PrP(BSE)) i

221 n of 2 log10 in PrP(263K) and 3 log10 in PrP(CWD).

222 Interestingly, PrP(CWD) was not demonstrable in these excretory tissues by

223 sensitivity than IHC in tissues with low PrP(CWD) burdens, including those that are IHC-negative.

224 At 3 MPE, PrP(CWD) replication had expanded to all systemic lymphoid t

225 days (1 and 3) postexposure, we observed PrP(CWD) seeding activity and follicular immunoreactivity in

226 Deer with highest levels of PrP(CWD) amplification in the brain had higher and more wide

227 s a significant step toward detection of PrP(CWD) in the body fluids or excreta of CWD-susceptible sp

228 ghly efficient in vitro amplification of PrP(CWD) is a significant step toward detection of PrP(CWD)

229 and monitored the tissue distribution of PrP(CWD) over the first 4 months of infection.

230 , is an effective assay for detection of PrP(CWD)in rectal biopsy specimens and other antemortem samp

231 etection of misfolded CWD prion protein (PrP(CWD)) by western blotting, ELISA, or immunohistochemistr

232 By 4 MPE, the PrP(CWD) burden in all lymphoid tissues had increased and ap

233 ciating putative follicular B cells with PrP(CWD).

234 ed and scored based on the apparent relative CWD burden.

235 advance in assessing the risks posed by shed CWD prions to animals as well as humans.

236 We show CWD uptake occurs in the oropharynx with initial prion r

237 Our results demonstrate that CWD can be efficiently transmitted utilizing Mte particl

238 These results demonstrate that CWD can be transmitted and adapted to the domestic cat,

239 ic amplification (sPMCA) to demonstrate that CWD prions can amplify in brain homogenates from several

240 by infectivity assays, they will imply that CWD prions have the potential to infect humans and that

241 These results indicate that CWD blood infectivity is cell associated and suggest a s

242 These results show that CWD can be transmitted and adapted to some species of ro

243 These findings suggest that CWD prions from elk, mule deer, and white-tailed deer ca

244 onversion of human PrP(C) but only after the CWD prion strain has been stabilized by successive passa

245 tional stability of PrP(Sc) differed for the CWD strains in a host-dependent manner.

246 had limited susceptibility to certain of the CWD inocula, as evidenced by incomplete attack rates and

247 ne affecting the intrinsic properties of the CWD prion.

248 ng treatment, and results indicated that the CWD prions were not altered by IND24, regardless of surv

249 vestigate the susceptibility of swine to the CWD agent following experimental oral or intracranial in

250 Therefore, CWD isolates from mule deer, white-tailed deer, and elk

251 CWD prions, although the species barrier to CWD infection is relatively high.

252 ibility of the domestic cat (Felis catus) to CWD infection experimentally.

253 early prion pathogenesis, we exposed deer to CWD prions and monitored the tissue distribution of PrP(

254 athogenesis, we exposed white-tailed deer to CWD prions by mucosal routes and performed serial necrop

255 hogen-mediated selection has occurred due to CWD.

256 Human exposure to CWD occurs through hunting activities and consumption of

257 We determined population exposure to CWD, genotyped 1,018 elk from five populations, and deve

258 o populations with no history of exposure to CWD.

259 addition of brain-derived lipid extracts to CWD prion brain or lymph node samples inhibited amyloid

260 tant role in the susceptibility of humans to CWD prions.

261 ble to draw several conclusions pertinent to CWD biology from our analyses: (i) the shedding of prion

262 otype, associated with partial resistance to CWD, was used to infect transgenic (tg) mice expressing

263 the inevitable exposure of these rodents to CWD prions, our intracerebral challenge results indicate

264 96 were found to differ in susceptibility to CWD infection.

265 deer PrP polymorphisms in susceptibility to CWD infection.

266 mucosa lesions may enhance susceptibility to CWD infections.

267 ect humans; however, human susceptibility to CWD is unknown.

268 tion substantially reduces susceptibility to CWD.

269 the cervid prion protein and susceptible to CWD (Tg(cerPrP)5037 mice) but lack CD21/35 expression co

270 Djungarian hamsters were not susceptible to CWD.

271 ole for B cells and platelets in trafficking CWD infectivity in vivo and support earlier tissue-based

272 nd infectious prions capable of transmitting CWD in saliva (by the oral route) and in blood (by trans

273 Accordingly, quinacrine-treated CWD prions were comprised of an altered PrP(Sc) conforma

274 IND24 may be a viable candidate for treating CWD in infected captive cervid populations and raise que

275 Two CWD strains that have distinct biological, biochemical,

276 etermined infectivity titers in fat from two CWD-infected deer.

277 ical CWD that are important to understanding CWD transmission and ecology.

278 f CWD in a region of northern Illinois using CWD surveillance in deer and soils data.

279 affic in vivo, including the manner by which CWD prions traffic from the gastrointestinal tract to th

280 ies remain regarding the mechanisms by which CWD prions traffic in vivo, including the manner by whic

281 ng epidemiological studies in areas in which CWD is endemic or not endemic.

282 ease-resistant prion protein associated with CWD.

283 ing in saliva; oral inoculation of deer with CWD-positive saliva resulted in 2.77 times the likelihoo

284 ironmental exposure or exposure to deer with CWD.

285 at this ability progressively increases with CWD spreading.

286 Populations infected with CWD for at least 30-50 y exhibited 132L allele frequenci

287 the incubation times for mice infected with CWD prions but had no effect on the survival of those in

288 dized transgenic (CerPrP) mice infected with CWD.

289 ore consistently than, those inoculated with CWD prions from deer brain.

290 Tg[CerPrP] mice were then inoculated with CWD via one of four routes (intracerebral, intravenous,

291 develop prion disease after inoculation with CWD prions from among nine different isolates after >500

292 aliva compared to that from inoculation with CWD-positive brain.

293 intracerebrally (i.c.) or orally (p.o.) with CWD-infected deer brain.

294 ation of the 132L allele in populations with CWD.

295 r species of epidemic-sympatric rodents with CWD.

296 tter agreement with Yp and Yw simulated with CWD (i.e. little bias and an RMSE of 12-19% of the absol

297 pared from CWD-positive deer with or without CWD-resistant genotypes were similar.

298 WST CWD produced PrP(Sc) amyloid plaques in the brain of the

299 owever, in transgenic mice, PrP(Sc) from WST CWD did not assemble into plaques, was highly soluble, a

300 D was approximately 150 days longer than WST CWD.