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.
Ehlin-Henriksson
Barbro
B
Microbiology and Tumour Biology Centre, Karolinska Institute, Stockholm, Sweden. barbro.ehlin-henriksson@mtc.ki.se
Mowafi
Frida
F
Klein
George
G
Nilsson
Anna
A
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