Inhibition of tumor necrosis factor-alpha transcription by Epstein-Barr virus.
Tumor necrosis factor-alpha (TNF-alpha), which is produced mainly by monocyte/macrophage cells, has diverse physiological functions on lymphoid cells. Moreover, it has been shown that TNF-alpha 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-alpha 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 inhibitory effect on TNF-alpha synthesis. These results suggest that infectious virus is necessary to obtain such an inhibitory effect. Analysis of TNF-alpha 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.
Gosselin
J
J
Department of Microbiology and Immunology, University of Montreal, Quebec, Canada.
Menezes
J
J
D'Addario
M
M
Hiscott
J
J
Flamand
L
L
Lamoureux
G
G
Oth
D
D
D000911:Antibodies, Monoclonal / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001483:Base Sequence; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011951:Receptors, Complement / Q000378:metabolism; D017464:Receptors, Complement 3d; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D007375:Interleukin-1; D009841:Oligonucleotides; D012333:RNA, Messenger; D011951:Receptors, Complement; D017464:Receptors, Complement 3d; D014409:Tumor Necrosis Factor-alpha