The ecology of chronic wasting disease in wildlife

Prions are misfolded infectious proteins responsible for a group of fatal neurodegenerative diseases termed transmissible spongiform encephalopathy or prion diseases. Chronic Wasting Disease (CWD) is the prion disease with the highest spillover potential, affecting at least seven Cervidae (deer) species. The zoonotic potential of CWD is inconclusive and cannot be ruled out. A risk of infection for other domestic and wildlife species is also plausible. Here, we review the current status of the knowledge with respect to CWD ecology in wildlife. Our current understanding of the geographic distribution of CWD lacks spatial and temporal detail, does not consider the biogeography of infectious diseases, and is largely biased by sampling based on hunters' cooperation and funding available for each region. Limitations of the methods used for data collection suggest that the extent and prevalence of CWD in wildlife is underestimated. If the zoonotic potential of CWD is confirmed in the short term, as suggested by recent results obtained in experimental animal models, there will be limited accurate epidemiological data to inform public health. Research gaps in CWD prion ecology include the need to identify specific biological characteristics of potential CWD reservoir species that better explain susceptibility to spillover, landscape and climate configurations that are suitable for CWD transmission, and the magnitude of sampling bias in our current understanding of CWD distribution and risk. Addressing these research gaps will help anticipate novel areas and species where CWD spillover is expected, which will inform control strategies. From an ecological perspective, control strategies could include assessing restoration of natural predators of CWD reservoirs, ultrasensitive CWD detection in biotic and abiotic reservoirs, and deer density and landscape modification to reduce CWD spread and prevalence.     

Inhibition of protease-resistant prion protein formation in a transformed deer cell line infected with chronic wasting disease

Chronic wasting disease (CWD) is an emerging transmissible spongiform encephalopathy (prion disease) of North American cervids, i.e., mule deer, white-tailed deer, and elk (wapiti). To facilitate in vitro studies of CWD, we have developed a transformed deer cell line that is persistently infected with CWD. Primary cultures derived from uninfected mule deer brain tissue were transformed by transfection with a plasmid containing the simian virus 40 genome. A transformed cell line (MDB) was exposed to microsomes prepared from the brainstem of a CWD-affected mule deer. CWD-associated, protease-resistant prion protein (PrP(CWD)) was used as an indicator of CWD infection. Although no PrP(CWD) was detected in any of these cultures after two passes, dilution cloning of cells yielded one PrP(CWD)-positive clone out of 51. This clone, designated MDB(CWD), has maintained stable PrP(CWD) production through 32 serial passes thus far. A second round of dilution cloning yielded 20 PrP(CWD)-positive subclones out of 30, one of which was designated MDB(CWD2). The MDB(CWD2) cell line was positive for fibronectin and negative for microtubule-associated protein 2 (a neuronal marker) and glial fibrillary acidic protein (an activated astrocyte marker), consistent with derivation from brain fibroblasts (e.g., meningeal fibroblasts). Two inhibitors of rodent scrapie protease-resistant PrP accumulation, pentosan polysulfate and a porphyrin compound, indium (III) meso-tetra(4-sulfonatophenyl)porphine chloride, potently blocked PrP(CWD) accumulation in MDB(CWD) cells. This demonstrates the utility of these cells in a rapid in vitro screening assay for PrP(CWD) inhibitors and suggests that these compounds have potential to be active against CWD in vivo.     

森林生态系统粗死木质残体碳储量研究进展

粗死木质残体(CWD)是森林生态系统重要的结构性与功能性单元,作为连接植被碳库与土壤碳库的关键纽带,对全球森林生态系统碳循环发挥着重要而独特的作用,越来越多的学者开始关注CWD碳储量相关研究。系统阐述了国内外CWD碳储量研究的发展历程、研究范围与基本特征等内容,总结概括了CWD体积测算、CWD碳浓度估算等碳计量相关方法的研究进展。通过梳理发现:国内外学者对CWD碳储量的研究仍处于初级阶段,主要集中于探讨不同树种、不同林龄、不同腐解等级、不同海拔、不同存在形式的森林CWD碳储量分布特征,而较少关注CWD碳库对土壤碳库和植被碳库的作用机制以及对未来气候变化的响应和反馈机制;CWD碳计量方法较为单一,普遍采用的是传统的"生物量-碳浓度法",而运用机器学习算法对CWD碳储量进行估算的研究尚不多见。此外,相对国外研究而言,国内研究主要局限于小尺度范围。文章据此提出未来CWD碳储量研究的发展方向:(1)拓展研究尺度,建立CWD碳储量长期观测体系;(2)深入开展不同森林生态系统CWD碳储量对气候变化的响应机制研究;(3)探索更加多元化的CWD碳储量计量方法;(4)深入探讨CWD碳库对土壤碳库与植被碳...     

Detection of PrPCWD in feces from naturally exposed Rocky Mountain elk (Cervus elaphus nelsoni) using protein misfolding cyclic amplification

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy affecting captive and free-ranging cervids. Currently, tests for CWD in live animals involve relatively invasive procedures to collect lymphoid tissue biopsies and examine them for CWD-associated, protease-resistant cervid prion protein (PrP(CWD)) detected by immunohistochemistry (IHC). We adapted an ultrasensitive prion detection system, protein misfolding cyclic amplification (PMCA), to detect PrP(CWD) in Rocky Mountain elk (Cervus elaphus nelsoni) feces. Our PMCA reproducibly detected a 1.2 × 10(7) dilution of PrP(CWD) (a 10% infected brain homogenate diluted 1.2 × 10(6)-fold into 10% fecal homogenates), equivalent to approximately 100 pg of PrP(CWD)/g of feces. We developed a semiquantitative scoring system based on the first PMCA round at which PrP(CWD) was detected and fit a nonlinear regression curve to our serial dilutions to correlate PMCA scores with known PrP(CWD) concentrations. We used this PMCA scoring system to detect PrP(CWD) and estimate its concentration in feces from free-ranging elk from Rocky Mountain National Park, Colorado. We compared our results to PrP(CWD) IHC of rectoanal mucosa-associated lymphoid tissue and obex from the same animals. The PMCA successfully detected PrP(CWD) in feces from elk that were positive by IHC, with estimated prion loads from 100 to 5,000 pg PrP(CWD)/g of feces. These data show for the first time PrP(CWD) in feces from naturally exposed free-ranging elk and demonstrate the potential of PMCA as a new, noninvasive CWD diagnostic tool to complement IHC.     

西双版纳热带季节雨林粗木质物残体储量及其空间分布

粗木质物残体(CWD)在森林生态系统的物质循环和碳动态中发挥着重要作用,但目前国内对热带地区CWD储量与其空间分布关系上的研究还处于起步阶段。对西双版纳1hm2热带季节雨林样地调查发现,≥10cm的粗木质物残体占森林总凋落物量的68.02%,其中45.72%的CWD处于腐解中后期。由于多数大径级的CWD分布于15°～25°的坡地上,且其饱和持水力随腐解等级的增加而上升,因此,CWD将有助于改善坡地生境下的水肥条件。CWD的分布受风向和本地湿热环境的影响,但掉落指向则更倾向于随机过程。CWD产生和分布上的普遍性有可能对森林生境异质性和生物多样性产生重大影响。     

Spatial epidemiology of chronic wasting disease in Wisconsin white-tailed deer

Chronic wasting disease (CWD) is a fatal, emerging disease of cervids associated with transmissible protease-resistant prion proteins. The potential for CWD to cause dramatic declines in deer and elk populations and perceived human health risks associated with consuming CWD-contaminated venison have led wildlife agencies to embark on extensive CWD control programs, typically involving culling to reduce deer populations. We characterized the spatial distribution of CWD in white-tailed deer (Odocoileus virginianus) in Wisconsin to facilitate CWD management. We found that CWD prevalence declined with distance from a central location, was locally correlated at a scale of 3.6 km, and was correlated with deer habitat abundance. The latter result is consistent with patterns expected for a positive relationship between density and prevalence of CWD. We recommend management activities focused on culling in geographic areas with high prevalence to have the greatest probability of removing infected individuals. Further research is needed to elucidate the factors involved in CWD spread and infection rates, especially the role of density-dependent transmission.     

The influence of nutrient loading,climate and water depth on nitrogen and phosphorus loss in shallow lakes: a pan-European mesocosm experiment

Coarse woody debris (CWD) represents a relatively stable habitat in many lakes with forested shorelines providing a living place for a wide range of species. The spatial complexity of CWD is recognized as an important factor promoting the abundance, diversity and productivity of littoral biota, mainly by providing shelters and moderating predator–prey interactions. However, little is as yet known on the response of different species to various levels of CWD complexity and the effects of the spatial arrangement of CWD on the connectivity between littoral populations. It is also unclear how CWD decay, which modifies the surface complexity of wood and the quality of food, affects the diversity of wood-associated species and trophic interactions. Further research is also needed to recognize the contribution of littoral wood to carbon sequestration and nutrient fluxes, considering factors affecting the CWD decay rate, such as wood species and environmental conditions. CWD resources are systematically depleted by shoreline development which leads to disruptions in the functioning of lake ecosystems. Attempts at restoring CWD habitat provided ambiguous effects on littoral species and therefore better understanding of the role of CWD in lake ecosystems is crucial to the development of successful restoration projects and effective management programmes.     

Nitrogen transformation rates are affected by cover soil type but not coarse woody debris application in reclaimed oil sands soils

Forest floor mineral soil mix (FMM) and peat mineral soil mix (PMM) are cover soils commonly used for reclamation of open‐pit oil sands mining disturbed land in northern Alberta, Canada; coarse woody debris (CWD) is another source of organic matter for land reclamation. We investigated net nitrogen (N) transformation rates in FMM and PMM cover soils near and away from CWD 4–6 years after oil sands reclamation. Monthly net nitrification and N mineralization rates varied over time; however, mean rates across the incubation periods and microbial biomass were greater (p < 0.05) in FMM than in PMM. Net N mineralization rates were positively related to soil temperature (p < 0.001) and microbial biomass carbon (p = 0.045). Net N transformation rates and inorganic N concentrations were not affected by CWD; however, the greater ¹⁵N isotope ratio of ammonium near CWD than away from CWD indicates that CWD application increased both gross N mineralization/nitrification (causing N isotope fractionation) and gross N immobilization (no isotopic fractionation). Microbial biomass was greater near CWD than away from CWD, indicating the greater potential for N immobilization near CWD. We conclude that (1) CWD application affected soil microbial properties and would create spatial variability and diverse microsites and (2) cover soil type and CWD application had differential effects on net N transformation rates. Applying FMM with CWD for oil sands reclamation is recommended to increase N availability and microsites.     

Alteration of the chronic wasting disease species barrier by in vitro prion amplification

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of cervids now detected in 19 states of the United States, three Canadian provinces, and South Korea. Whether noncervid species can be infected by CWD and thereby serve as reservoirs for the infection is not known. To investigate this issue, we previously used serial protein misfolding cyclic amplification (sPMCA) to demonstrate that CWD prions can amplify in brain homogenates from several species sympatric with cervids, including prairie voles (Microtus ochrogaster) and field mice (Peromyscus spp.). Here, we show that prairie voles are susceptible to mule deer CWD prions in vivo and that sPMCA amplification of CWD prions in vole brain enhances the infectivity of CWD for this species. Prairie voles inoculated with sPMCA products developed clinical signs of TSE disease approximately 300 days prior to, and more consistently than, those inoculated with CWD prions from deer brain. Moreover, the deposition patterns and biochemical properties of protease-resistant form of PrP (PrP(RES)) in the brains of affected voles differed from those in cervidized transgenic (CerPrP) mice infected with CWD. In addition, voles inoculated orally with sPMCA products developed clinical signs of TSE and were positive for PrP(RES) deposition, whereas those inoculated orally with deer-origin CWD prions did not. These results demonstrate that transspecies sPMCA of CWD prions can enhance the infectivity and adapt the host range of CWD prions and thereby may be useful to assess determinants of prion species barriers.     

溪流粗木质残体的生态学研究进展

粗木质残体（CWD）是森林或溪流生态系统中残存的超过一定直径大小的站杆、倒木、枝桠及根系等死木质物的总称,溪流CWD对于溪流生态系统的稳定,水生生物多样性,河槽形态及其变化过程有着重要的作用。对溪流CWD的产生和分类,溪流CWD对于溪流生态系统的稳定,水生生物多样性,河槽形态及其变化过程有着重要的作用。对溪流CWD的产生和分类,溪流CWD贮量,分布和动态,以及溪流CWD的功能和管理分别进行了总结,并指出应尽快在国内开展溪流CWD的研究和管理。     

The Effect of a Copper Smelter Emissions on the Stock and Decomposition of Coarse Woody Debris in Spruce and Fir Woodlands

We have studied the share of coarse woody debris (CWD) reserves at different decay classes in the spruce and fir woodland within the impact area of aerial pollution from the Middle Ural Copper Smelter (Revda, Sverdlovsk oblast). Control and impact areas slightly differ in total reserves and number of trunks of CWD (sum of standing and fallen dead wood). However, the number of CWD tends to grow in proximity to the plant. The mechanisms involved in CWD-reserve formation differ between impact and control sites. A larger number of relatively thin trunks prevail in CWD reserves of impact sites when compared to the lower number of thick trunks at control sites. The CWD share of 30% in the total number of dead and living trees did not differ across pollution loads. However, the share of CWD reserves in total stock is 1.9 times higher near the plant than at the control site. The share of logs at the initial stages of decomposition (first and second decay classes) is 3.2 times higher in terms of CWD number and 4.2 times higher in terms of CWD reserves than at the control sites. This points to the strong inhibition of CWD decomposition. The pattern of decay classes of all sizes of fallen trees significantly differs in volume across pollution zones.     

Impacts of retention felling on coarse woody debris (CWD) in mature boreal spruce forests in Finland

We studied the immediate changes in pre-treatment coarse woody debris (CWD) after retention felling and mechanical site preparation (scarification) in mature Picea abies-dominated boreal forest. Retention felling and scarification were hypothetised to affect the amount of CWD. The disturbance caused to CWD was assumed to depend on species and decay class. Logs were inventoried before fellings, after fellings, and after scarification, estimating the damage percentage for each log. After felling, 7.8% of the total pre-treatment volume of CWD was destroyed in the felled area. After scarification, the decline from pre-treatment volume was 67.6% in the felled area. The amount of CWD decreased also inside the retention tree groups; in the 1st post-treatment season, 4.6% was destroyed of the pre-treatment volume and 20% in the 2nd season. Of the retained trees, 40% were uprooted by the end of the 2nd season. If the majority of the initial downed CWD is destroyed by scarification, as our results show, we can estimate that since scarification became a widely used regeneration method in the 1960s, at least from 4 to 6 million m³ of CWD has already been destroyed in Finland. The role of CWD as a key element for biodiversity in boreal forest is generally accepted, which has led to retention of trees in fellings instead of clear felling. We suggest that at least as important as leaving trees in order to maintain continuum in CWD and species diversity is to preserve existing CWD in fellings over the regeneration phase. This can be done using less destructive harvesting methods, reduced use of scarification and placing retention tree groups in patches with high amounts of CWD.     

Benchmarks and predictors of coarse woody debris in native forests of eastern Australia

Fallen coarse woody debris (CWD) is critical to forest biodiversity and function. Few studies model factors that influence CWD availability, although such investigations are critically needed to inform sustainable forest management. We assess benchmark levels of CWD in unharvested native forests and those harvested for timber, across a range of forests in north‐east New South Wales, Australia. We found timber‐harvesting was the dominant driver of CWD, with almost double the count (pieces ha^?1) and volume (m³ ha^?1) of total CWD in selectively harvested than unharvested sites. This pattern was consistent across wet and dry forest types. Harvested sites had greater counts of hollow‐bearing logs, and greater volumes of small and medium‐sized CWD (15–50 cm diameter) than unharvested sites. There was no effect of harvesting on the volume of large CWD (>51 cm diameter). Total volumes of CWD (>15 cm diameter) varied from 114 to 166 m³ ha^?1. We found few differences in CWD counts and volumes between forest types, with grassy woodlands and forests containing less CWD than other dry and shrubby forest types, reflecting lower potential input rates. The CWD levels recorded here are similar to those recorded in dry and wet sclerophyll forests elsewhere in Australia and are typical of global estimates for ‘old growth’ forests. Using general linear models we captured up to 57% of the variation in CWD across sites, and found that timber harvesting, topography and the numbers of standing hollow‐bearing and dead trees were significant predictors of CWD. Values for unharvested forest provide a benchmark that could be used to inform retention guidelines for CWD in managed forests in this region. Further assessment of the effect of repeat timber harvesting is needed to fully understand its impact on CWD dynamics, especially if forest residues resulting from timber harvesting are removed from native forests for bioenergy production.     

Coarse woody debris modifies surface soils of degraded temperate eucalypt woodlands

Aims

Reintroductions of coarse woody debris (CWD) to Australia’s temperate eucalypt woodlands have been proposed to address the paucity of CWD in these landscapes. This study aimed to quantify the effects of CWD on surface soils.

Methods

Values of C, N, C:N, P, NO₃ ^?, NH₄ ⁺, pH and electrical conductivity (EC) were measured adjacent to, and at reference distances from CWD. Soils were measured at depths of 0–1 cm, 1–3 cm and 3–5 cm for 12 individual CWD samples of varying decay classes and diameters. A linear mixed model was used to test the effects of the presence of CWD, soil depth and CWD decay class and diameter.

Results

Significantly larger values for C, N, C:N, P, NO₃ ^?, EC, and significantly smaller values for pH were found adjacent to CWD. The greatest impact of CWD was on the upper most surface soil. CWD decay class and diameter had little influence on the measured soil characteristics.

Conclusion

This is the first quantitative determination of the effects of eucalypt CWD on woodland soils in Australia. The effect of added CWD is rapid, occurring after just 2 years. The results suggest that the effects are due to the structural properties of CWD.     

广州三种森林粗死木质残体（CWD）的储量与分解特征

粗死木质残体(Coarse Woody Debris, CWD)对森林生态系统的稳定性具有不可忽视的贡献.对广州3种森林CWD的储量与分解特征进行了调查分析,结果表明:(1)CWD储量及其与相应森林总生物量比值均表现为常绿阔叶林>针阔混交林>针叶林;枯立木与倒木为CWD的主要成分,其中,针叶CWD主要物种为马尾松(Pinus massonianai),阔叶CWD物种主要为荷木(Schima superba)与黄杞(Engelhardtia chrysolepis)等.(2)CWD径级主要集中在<10cm的范围内,存在状态主要为中级腐烂状态,干扰与竞争是3种森林CWD产生的主要因素.(3)针叶林、针阔混交林与常绿阔叶林CWD的分解常数k分别为0 0244、0.0407和0.0487,即分解速率为常绿阔叶林>混交林>针叶林;随着CWD的分解,N、P与木质素的含量逐渐升高,C、C/N与木质素/N呈降低趋势.     

呼中林区与呼中自然保护区森林粗木质残体储量的比较

采用样线法研究了人为干扰对大兴安岭呼中林区粗木质残体(Coarse woody debris, CWD)储量的影响。结果表明, 未受人为干扰的呼中自然保护区中CWD变化范围集中在5.92~43.53 m³·hm^-2, 受到人为干扰的呼中林区中CWD变化范围集中在12.70~47.59 m³·hm^-2之间。人为干扰对混交林和针叶林的CWD储量影响显著, 而对阔叶林CWD储量影响不显著。人为干扰增加了混交林CWD储量, 减少了针叶林CWD储量, 同时减少了枯立木的数量, 增加了高度腐烂的CWD的比例。对兴安落叶松各林型的分析表明, 人为干扰条件下CWD储量(8.20~25.60 m³·hm^-2)是未受干扰条件下CWD储量(18.70~36.99 m³·hm^-2)的1/4~1/3。为促使采伐后的森林能维持原始林粗木质残体的结构特征, 建议保留采伐剩余物以维持一定储量的CWD。     

Habitat availability in forests and clearcuts for saproxylic beetles associated with aspen

To maintain biodiversity in managed, boreal forest in Scandinavia, aspen trees (Populus tremula) are often retained at clearcutting. In this study, the habitat availability for beetles associated with aspen coarse woody debris (CWD) was predicted for forests and clearcuts with a model of CWD dynamics. Habitat requirements of eight beetle species (Agathidium bicolor, Cerylon ferrugineum, Cyphaea curtula, Endomychus coccineus, Homalota plana, Mycetophagus fulvicollis, Ptilinus fuscus and Xylotrechus rusticus) were obtained from their occurrence patterns in relation to characteristics of CWD objects in forest and on clearcuts in a study landscape in central Sweden. Three species were more frequent in forest and three at clearcuts. Five species increased with increasing girth of the CWD. Three were more frequent on standing CWD, and two on lying CWD. From the same study area, we also obtained field data on the recruitment of CWD (i.e., tree mortality) and amounts of different types of CWD. Annual tree mortality of aspen was higher for recent clearcuts (6.3%) compared with older clearcuts (1.1%). For all species, the habitat availability was higher on clearcuts, because enhanced tree mortality increased the amount of recently dead CWD. As a conclusion, green-tree retention of aspen is a conservation effort that is beneficial for species associated with aspen CWD.     

From Models to Measurements: Comparing Downed Dead Wood Carbon Stock Estimates in the U.S. Forest Inventory

The inventory and monitoring of coarse woody debris (CWD) carbon (C) stocks is an essential component of any comprehensive National Greenhouse Gas Inventory (NGHGI). Due to the expense and difficulty associated with conducting field inventories of CWD pools, CWD C stocks are often modeled as a function of more commonly measured stand attributes such as live tree C density. In order to assess potential benefits of adopting a field-based inventory of CWD C stocks in lieu of the current model-based approach, a national inventory of downed dead wood C across the U.S. was compared to estimates calculated from models associated with the U.S.’s NGHGI and used in the USDA Forest Service, Forest Inventory and Analysis program. The model-based population estimate of C stocks for CWD (i.e., pieces and slash piles) in the conterminous U.S. was 9 percent (145.1 Tg) greater than the field-based estimate. The relatively small absolute difference was driven by contrasting results for each CWD component. The model-based population estimate of C stocks from CWD pieces was 17 percent (230.3 Tg) greater than the field-based estimate, while the model-based estimate of C stocks from CWD slash piles was 27 percent (85.2 Tg) smaller than the field-based estimate. In general, models overestimated the C density per-unit-area from slash piles early in stand development and underestimated the C density from CWD pieces in young stands. This resulted in significant differences in CWD C stocks by region and ownership. The disparity in estimates across spatial scales illustrates the complexity in estimating CWD C in a NGHGI. Based on the results of this study, it is suggested that the U.S. adopt field-based estimates of CWD C stocks as a component of its NGHGI to both reduce the uncertainty within the inventory and improve the sensitivity to potential management and climate change events.     

Regulatory T cells in patients with Whipple's disease

Classical Whipple's disease (CWD) is caused by chronic infection with Tropheryma whipplei that seems to be associated with an underlying immune defect. The pathognomonic hallmark of CWD is a massive infiltration of the duodenal mucosa with T. whipplei-infected macrophages that disperse systemically to many other organ systems. An alleviated inflammatory reaction and the absence of T. whipplei-specific Th1 reactivity support persistence and systemic spread of the pathogen. In this article, we hypothesized that regulatory T cells (T(reg)) are involved in immunomodulation in CWD, and we asked for the distribution, activation, and regulatory capacity of T(reg) in CWD patients. Whereas in the lamina propria of CWD patients before treatment numbers of T(reg) were increased, percentages in the peripheral blood were similar in CWD patients and healthy controls. However, peripheral T(reg) of CWD patients were more activated than those of controls. Elevated secretion of IL-10 and TGF-β in the duodenal mucosa of CWD patients indicated locally enhanced T(reg) activity. Enhanced CD95 expression on peripheral memory CD4(+) T cells combined with reduced expression of IFN-γ and IL-17A upon polyclonal stimulation by CD4(+) cells from untreated CWD patients further hinted to T(reg) activity-related exhaustion of effector CD4(+) T cells. In conclusion, increased numbers of T(reg) can be detected within the duodenal mucosa in untreated CWD, where huge numbers of T. whipplei-infected macrophages are present. Thus, T(reg) might contribute to the chronic infection and systemic spread of T. whipplei in CWD but in contrast prevent mucosal barrier defect by reducing local inflammation.     

Strain fidelity of chronic wasting disease upon murine adaptation

Chronic wasting disease (CWD), a prion disease of deer and elk, is highly prevalent in some regions of North America. The establishment of mouse-adapted CWD prions has proven difficult due to the strong species barrier between mice and deer. Here we report the efficient transmission of CWD to transgenic mice overexpressing murine PrP. All mice developed disease 500 +/- 62 days after intracerebral CWD challenge. The incubation period decreased to 228 +/- 103 days on secondary passage and to 162 +/- 6 days on tertiary passage. Mice developed very large, radially structured cerebral amyloid plaques similar to those of CWD-infected deer and elk. PrP(Sc) was detected in spleen, indicating that murine CWD was lymphotropic. PrP(Sc) glycoform profiles maintained a predominantly diglycosylated PrP pattern, as seen with CWD in deer and elk, across all passages. Therefore, all pathological, biochemical, and histological strain characteristics of CWD appear to persist upon repetitive serial passage through mice. These findings indicate that the salient strain-specific properties of CWD are encoded by agent-intrinsic components rather than by host factors.