Inhibition of tumor necrosis factor‐α transcription by Epstein‐Barr virus

Abstract

Tumor necrosis factor‐α (TNF‐α), which is produced mainly by monocyte/macrophage cells, has diverse physiological functions on lymphoid cells. Moreover, it has been shown that TNF‐α exhibits antiviral activities. Here we report that Epstein‐Barr virus (EBV), a B lymphotropic human herpes virus that interacts intimately with the immune system, exerts a strong inhibitory effect on TNF‐α production by lipopolysaccharide‐treated peripheral blood leukocytes as well as by monocytic cell lines, HL‐60 and U‐937. Flow cytometric analysis following staining with OKB7 monoclonal antibody showed that about 20% of cells from these monocytic lines express the CR2 antigen. Direct binding of fluorescein isothiocyanate‐labeled EBV indicated that the virus binds to approximately 22% of cells of both monocytic lines. However, no virus‐specific antigens were detected in the infected cells by immunofluorescence, suggesting that the infection was of the abortive type. The use of UV‐ or heat‐inactivated EBV and EBV treated with neutralizing antibodies resulted in the abrogation of the EBV inhibitory effect on TNF‐α synthesis. These results suggest that infectious virus is necessary to obtain such an inhibitory effect. Analysis of TNF‐α mRNA by polymerase chain reaction amplification indicated that the EBV suppressive effect is manifested at the transcriptional level. In contrast, EBV did not inhibit interleukin 1 mRNA production by these cells. These results indicate that EBV interacts directly with monocytes/macrophages to exert its immunomodulatory effect.