B Cells and Platelets Harbor Prion Infectivity in the Blood of Deer Infected with Chronic Wasting Disease
B Cells and Platelets Harbor Prion Infectivity in the Blood of Deer Infected with Chronic Wasting Disease
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DOI：
10.1128/jvi.02169-09
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发表时间：
2010-05-01
影响因子：
5.4
通讯作者：
Hoover, Edward A.
中科院分区：
文献类型：
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作者：
Mathiason, Candace K.;Hayes-Klug, Jeanette;Hoover, Edward A.
许多传染性海绵状脑病（TSE）存在通过输血传播朊病毒的大量证据。确定哪种细胞表型负责贩运传染性对我们了解朊病毒的传播以及从血液制品中检测和消除它们具有重要意义。我们对本地白尾鹿和转基因颈化小鼠进行了生物测定研究，以确定(i)慢性消耗性疾病（CWD）血液传染性是否与血液中细胞与无细胞/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（+）单核血细胞表型是否携带感染性朊病毒。接种CWD+供体鹿的单核细胞部分的4只鹿在接种后19个月均呈PrPCWD阳性，而接种同一来源的无细胞血浆的4只鹿均未发生朊病毒感染。接种B细胞的4只鹿和接受CWD+供体鹿血小板的4只鹿中的3只鹿在接种后6个月内均呈PrPCWD阳性，而在19个月的观察后，接受血液CD14（+）单核细胞的4只鹿均未出现CWD感染的证据（免疫组织化学和Western blot分析）。Tg（CerPrP）小鼠生物测定结果与天然宫颈宿主的结果一致。这些结果表明，CWD血液传染性与细胞相关，并提示B细胞和血小板在体内转运CWD传染性中发挥重要作用，并支持早期将卵泡B细胞与PrPCWD联系起来的基于组织的研究。CWD感染与白细胞亚群的定位可能有助于提高CWD和其他tse的血液诊断分析的敏感性。
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 PrPCWD 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 PrPCWD 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 PrPCWD. Localization of CWD infectivity with leukocyte subpopulations may aid in enhancing the sensitivity of blood-based diagnostic assays for CWD and other TSEs.