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在感染慢性消瘦病的鹿的血液中,B 细胞和血小板携带朊病毒感染性。

B cells and platelets harbor prion infectivity in the blood of deer infected with chronic wasting disease.

机构信息

Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA.

出版信息

J Virol. 2010 May;84(10):5097-107. doi: 10.1128/JVI.02169-09. Epub 2010 Mar 10.

Abstract

Substantial evidence for prion transmission via blood transfusion exists for many transmissible spongiform encephalopathy (TSE) diseases. Determining which cell phenotype(s) is responsible for trafficking infectivity has important implications for our understanding of the dissemination of prions, as well as their detection and elimination from blood products. We used bioassay studies of native white-tailed deer and transgenic cervidized mice to determine (i) if chronic wasting disease (CWD) blood infectivity is associated with the cellular versus the cell-free/plasma fraction of blood and (ii) in particular if B-cell (MAb 2-104(+)), platelet (CD41/61(+)), or CD14(+) monocyte blood cell phenotypes harbor infectious prions. All four deer transfused with the blood mononuclear cell fraction from CWD(+) donor deer became PrP(CWD) positive by 19 months postinoculation, whereas none of the four deer inoculated with cell-free plasma from the same source developed prion infection. All four of the deer injected with B cells and three of four deer receiving platelets from CWD(+) donor deer became PrP(CWD) positive in as little as 6 months postinoculation, whereas none of the four deer receiving blood CD14(+) monocytes developed evidence of CWD infection (immunohistochemistry and Western blot analysis) after 19 months of observation. Results of the Tg(CerPrP) mouse bioassays mirrored those of the native cervid host. These results indicate that CWD blood infectivity is cell associated and suggest a significant role for B cells and platelets in trafficking CWD infectivity in vivo and support earlier tissue-based studies associating putative follicular B cells with PrP(CWD). Localization of CWD infectivity with leukocyte subpopulations may aid in enhancing the sensitivity of blood-based diagnostic assays for CWD and other TSEs.

摘要

大量证据表明,输血可传播许多传染性海绵状脑病(TSE)。确定负责运输感染性的细胞表型对于我们理解朊病毒的传播以及从血液产品中检测和消除朊病毒具有重要意义。我们使用天然白尾鹿和转基因鹿化小鼠的生物测定研究来确定(i)慢性消耗病(CWD)血液感染性是否与血液的细胞部分还是无细胞/血浆部分相关,以及(ii)特别是 B 细胞(MAb 2-104(+))、血小板(CD41/61(+))或 CD14(+)单核细胞是否携带感染性朊病毒。用来自 CWD(+)供体鹿的血液单个核细胞部分输注的四只鹿在接种后 19 个月均变为 PrP(CWD)阳性,而来自同一来源的无细胞血浆接种的四只鹿均未发生朊病毒感染。用 B 细胞和来自 CWD(+)供体鹿的血小板接种的四只鹿中的四只在接种后 6 个月内变为 PrP(CWD)阳性,而用来自 CWD(+)供体鹿的血液 CD14(+)单核细胞接种的四只鹿在观察 19 个月后均未出现 CWD 感染的证据(免疫组织化学和 Western blot 分析)。Tg(CerPrP)小鼠生物测定的结果与天然鹿宿主的结果相似。这些结果表明,CWD 血液感染性与细胞相关,并表明 B 细胞和血小板在体内运输 CWD 感染性方面具有重要作用,并支持更早的基于组织的研究将推定的滤泡 B 细胞与 PrP(CWD)相关联。将 CWD 感染性与白细胞亚群定位可能有助于提高基于血液的 CWD 和其他 TSE 诊断检测的敏感性。

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