Epstein-Barr virus infection negatively impacts the CXCR4-dependent migration of tonsillar B cells.
The primary Epstein-Barr virus (EBV) infection occurs in the oropharynx, where the virus infects B cells and subsequently establishes latency in the memory B-cell compartment. EBV has previously been shown to induce changes in the cell surface expression of several chemokine receptors in cell lines and the transfection of EBNA2 or LMP1 into a B-cell-lymphoma-derived cell line decreased the expression of CXCR4. We show that in vitro EBV infection reduces the expression of CXCR4 on primary tonsil B cells already 43 hr after infection. Furthermore, EBV infection affects the chemotactic response to stromal cell-derived factor (SDF-1)alpha/CXCL12, the ligand for CXCR4, with a reduction of SDF-1alpha-induced migration. To clarify whether this reduced migration is EBV-specific or a consequence of cell activation, tonsillar B cells were either infected with EBV, activated with anti-CD40 and interleukin-4 (IL-4) or kept in medium. Activation by anti-CD40 and IL-4 decreased the CXCR4 expression but the CD40 + IL-4-stimulated cells showed no reduction of chemotactic efficacy. Our finding suggests that changing the SDF-1alpha response of the EBV-infected B cells may serve the viral strategy by directing the infected cells into the extrafollicular areas, rather than retaining them in the lymphoepithelium.
Microbiology and Tumour Biology Centre, Karolinska Institute, Stockholm, Sweden. barbro.ehlin-henriksson@mtc.ki.se
Barbro
B
Ehlin-Henriksson
Frida
F
Mowafi
George
G
Klein
Anna
A
Nilsson
D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D014066:Palatine Tonsil / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000276:immunology*; D014764:Viral Proteins
D019013:CD40 Antigens; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C402641:EBNA-2 protein, Human herpesvirus 4; D019309:Epstein-Barr Virus Nuclear Antigens; D019718:Receptors, CXCR4; D014764:Viral Proteins; D015847:Interleukin-4