Hematopoietic cells from CD155-transgenic mice express CD155 and support poliovirus replication ex vivo

Hematopoietic cells from CD155-transgenic mice express CD155 and support poliovirus replication ex vivo
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DOI:
10.1006/mpat.2000.0386
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发表时间:
2000-10-01
影响因子:
3.8
通讯作者:
Eberle, KE
Eberle, KE
中科院分区:
医学3区
文献类型:
--
作者:
Freistadt, MS;Eberle, KE

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尽管鉴定了脊髓灰质炎病毒(PV)受体(CD 155),但该分子介导麻痹性疾病的机制仍不清楚。尚未回答的问题包括CD 155在人体组织中的定位,支持第一轮复制的细胞的性质,非神经复制位点的身份,以及进入CNS的途径。在早期的研究中,我们发现CD 155在原代人单核细胞上表达,并且这些细胞在没有预先培养的情况下支持低水平但具有统计学显著性的离体PV复制。我们假设单核细胞支持PV在体内的复制,并且它们有助于发病机制。在目前的研究中,我们测试了CD 155转基因小鼠造血细胞是否表达细胞表面CD 155,以及这些细胞是否支持PV复制。我们发现,大多数单核细胞/巨噬细胞从腹腔冲洗表达CD 155。此外,26-32%的CD 155转基因骨髓和脾细胞在单核细胞/巨噬细胞、T细胞和造血前体细胞上表达CD 155。各种组织支持PV复制而无需预培养,然而,用巯基乙酸盐预培养或预处理小鼠增加了病毒产量。这些结果与来自人细胞的结果一致,并且表明CD 155转基因小鼠模型有助于理解造血细胞在PV发病机制中的作用。(C)北京大学出版社.
Despite identification of the poliovirus (PV) receptor (CD155), mechanisms by which this molecule mediates paralytic disease remain obscure. Unanswered questions include CD155 localization in human tissues, the nature of cells supporting the first round of replication, identity of nonneural replication sites, and route of entry into the CNS. In earlier work, we showed that CD155 is expressed on primary human monocytes and that these cells support low, but statistically significant, levels of PV replication ex vivo without prior culturing. We hypothesize that monocytes support PV replication in vivo and that they contribute to pathogenesis. In the current study, we tested whether CD155-transgenic mouse hematopoietic cells express cell surface CD155 and whether these cells support PV replication. We found that the majority of monocyte/macrophages from peritoneal washes express CD155. In addition, 26-32% of CD155-transgenic bone marrow and spleen cells express CD155 on monocyte/macrophages, T cells and hematopoietic precursor cells. Various tissues supported PV replication without pre-culturing, however, pre-culturing or pre-treatment of mice with thioglycollate increased virus yield. These results are consistent with those from human cells and suggest that the CD155 transgenic mouse model is useful to help understand the role of hematopoietic cells in PV pathogenesis. (C) 2000 Academic Press.