Division of Viral Disease and Epidemiology, National Institute of Animal Health, National Agriculture and Food Research Organization, 3-1-5 Kannondai, Tsukuba, Ibaraki, 305-0856, Japan.
Division of Animal Breeding and Reproduction Research, Institute of Livestock and Grassland Science, National Agriculture and Food Research Organization, 2 Ikenodai, Tsukuba, Ibaraki, 305-0901, Japan.
Vet Microbiol. 2020 Mar;242:108598. doi: 10.1016/j.vetmic.2020.108598. Epub 2020 Jan 28.
Bovine leukemia virus (BLV) causes a lymphoproliferative disease in cattle and is transmitted horizontally and vertically via infected lymphocytes. Although transplacental infection is considered the predominant route of vertical transmission of BLV, the molecular mechanisms of this process remain to be elucidated. Notably, how BLV passes through the blood-placental barrier remains unclear, given that BLV is transmitted primarily by cell-to-cell contact. One hypothesis is that B cell migration to the placenta may be induced by certain endometrium-expressed chemokines. To test this hypothesis, we performed an in vitro cell migration assay using bovine B cell lines and endometrial epithelial cells. Cell migration assays showed that two bovine B cell lines, BL2M3 and BL3.1 cells, were attracted to the supernatant of bovine endometrial epithelial cells (BEnEpCs). Quantitative real-time RT-PCR showed that expression levels of mRNAs encoding the chemokines CCL2 and CXCL10 were higher in BEnEpCs than in MDBK cells. Additionally, an inhibition assay using immune serum against CCL2 and CXCL10 showed suppression of migration of bovine B cell lines. A syncytium assay showed that cells expressing BLV envelope (Env) protein fused with BEnEpCs. Here we found that bovine B cells are attracted by chemokines produced in the endometrium and that cells expressing BLV Env protein fused with endometrium epithelial cells. These results explain part of the molecular mechanism of transplacental transmission during BLV infection, although further analysis will be required. Advances in these areas are expected to contribute to controlling the spread of BLV.
牛白血病病毒（BLV）可引起牛的淋巴组织增生性疾病，并通过受感染的淋巴细胞水平和垂直传播。虽然胎盘感染被认为是 BLV 垂直传播的主要途径，但该过程的分子机制仍有待阐明。值得注意的是，由于 BLV 主要通过细胞间接触传播，因此 BLV 如何穿过胎盘血屏障尚不清楚。有一种假设是，某些子宫内膜表达的趋化因子可能会诱导 B 细胞迁移到胎盘。为了验证这一假设，我们使用牛 B 细胞系和子宫内膜上皮细胞进行了体外细胞迁移测定。细胞迁移测定表明，两种牛 B 细胞系 BL2M3 和 BL3.1 细胞被牛子宫内膜上皮细胞（BEnEpCs）的上清液吸引。实时定量 RT-PCR 显示，趋化因子 CCL2 和 CXCL10 的编码 mRNA 在 BEnEpCs 中的表达水平高于 MDBK 细胞。此外，使用针对 CCL2 和 CXCL10 的免疫血清进行的抑制测定表明，牛 B 细胞系的迁移受到抑制。合胞体测定显示，表达与 BEnEpCs 融合的 BLV 包膜（Env）蛋白的细胞。在这里，我们发现牛 B 细胞被子宫内膜产生的趋化因子吸引，并且表达与子宫内膜上皮细胞融合的 BLV Env 蛋白的细胞。这些结果解释了 BLV 感染期间胎盘传播的部分分子机制，但需要进一步分析。这些领域的进展有望有助于控制 BLV 的传播。
