The chemokines CCL2 and CXCL10 produced by bovine endometrial epithelial cells induce migration of bovine B lymphocytes, contributing to transuterine transmission of BLV infection

• Published in: Veterinary microbiology 2020-03, Vol.242, p.108598-108598, Article 108598
• Main Authors: Andoh, Kiyohiko, Nishimori, Asami, Sakumoto, Ryosuke, Hayashi, Ken-Go, Hatama, Shinichi
• Format: Article
• Language: English
• Subjects: BLV; Bovine leukosis; Cell adhesion & migration; Chemokine; Chemokines; CXCL10 protein; Endometrial epithelial cells; Endometrium; Env; Epithelial cells; Hypotheses; Immune serum; Immunoproliferative diseases; Infections; Leukocyte migration; Lymphocytes; Lymphocytes B; Molecular modelling; Monocyte chemoattractant protein 1; Placenta; Polymerase chain reaction; Syncytium; Viral envelope proteins
• ISSN: 0378-1135; 1873-2542
• DOI: 10.1016/j.vetmic.2020.108598

•Bovine leukemia virus (BLV) infects bovine B lymphocytes and is transmitted primarily by cell-to-cell contact.•Chemokines produced by bovine endometrial epithelial cells induce migration of bovine B lymphocytes into the endometrium.•CCL2 and CXCL10 were major attractants for migration of bovine B lymphocytes.•Cells expressing BLV Env protein fused with endometrial epithelial cells, implying that BLV can be transmitted to the placenta.•These findings show part of the molecular mechanism of transplacental infection by BLV. 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.