Inflammatory chemokine receptors in Epstein–Barr virus infection

Chemokines transmit signals via chemokine receptors (G-protein coupled cell-surface receptors) and thus the chemokine-receptor network controls immune responses in a body and directs migration of cells. Chemokine receptors CCR1, CCR2, CCR3, and CCR5 are the CC-receptors of the one protein-sequence-homology cluster. They share responses to the multiply inflammatory chemokines. Earlier, we have demonstrated that infection of B cells, isolated from the peripheral blood (PB) of healthy donors, with Epstein–Barr virus (EBV) up-regulates chemokine receptors CCR1 and CCR2B in the course of infection and in established lymphoblastoid cell lines (LCLs). EBV, a DNA gamma-1 herpes virus (human herpes virus 4), can infect B lymphocytes in vitro and immortalize them transforming into lymphoblasts, which express the EBV latency III program genes. EBV is associated with various types of B-cell malignancies, including Burkitt lymphoma (BL). All endemic BL tumors are carrying EBV. The study was designed in order to find out whether expression of CCR1, CCR2, CCR3, and CCR5 is linked to the EBV latency program in B cells. Fifteen BL cell lines (11 EBV-carrying and 4 EBV-negative) and 2 LCLs were analyzed for expression of CCR1, CCR2, CCR3, CCR5 and EBV latency genes, EBNA2, LMP1, and LMP2A, using duplex or real-time RT-PCR, Western blot, and flow cytometry analyses. The CCR3 and CCR5 mRNA expression was not detected in the study cell lines. High levels of CCR1 and CCR2B mRNA and protein expression were determined in LCLs and BL cell lines with the EBV latency III program. We suggest that expression of CCR1 and CCR2B in BL cells play a role in distribution of malignant cells in a body. Both chemokine receptors could be considered as prognostic markers of BL pathogenesis. The studies were funded by the Latvian Council of Science projects No.651/2014 and No.lzp-2018/1-0156.