Inhibition of macrophage inflammatory protein-1 alpha production by Epstein-Barr virus.
Infection with Epstein-Barr virus (EBV) exerts substantially immunomodulating activities in vitro and in vivo. In this context, EBV-induced chemokine production and the influence of EBV on this highly redundant system of inflammatory proteins have hardly been investigated. This study analyzed the production of interleukin-8, RANTES, monocyte chemotactic protein-1, and macrophage inflammatory protein-1 alpha (MIP-1 alpha) on EBV infection of peripheral blood mononuclear cells from immune EBV-seropositive (EBV(+)) and noninfected EBV-seronegative (EBV(-)) individuals. EBV failed to induce the production of MIP-1 alpha in EBV(+) as well as EBV(-) individuals, whereas the other chemokines studied were readily expressed. Moreover, EBV completely down-regulated lipopolysaccharide (LPS)- and phytohemagglutinin-induced MIP-1 alpha production up to 4 hours after induction. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of EBV- and LPS-stimulated cultures revealed that EBV inhibited MIP-1 alpha production on the transcriptional level. This effect was abolished by addition of antiglycoprotein (gp)350/220, a monoclonal antibody against EBV's major envelope glycoprotein, which mediates binding of the virus to the EBV receptor, CD21. However, recombinant gp350/220 protein alone did not inhibit the LPS-induced MIP-1 alpha production, indicating that infection of the target cell is indispensable for this effect. In summary, we demonstrate a new immunomodulating activity of EBV on the chemokine system that probably helps the virus to evade the host's immune system favoring lifelong infection.
Jabs
Wolfram J
WJ
First Department of Medicine, Division of Nephrology, University of Lübeck School of Medicine, Lübeck, Germany. wjabs@gmx.de
Wagner
Hans J
HJ
Maurmann
Susanne
S
Hennig
Holger
H
Kreft
Burkhard
B
D000914:Antibodies, Viral / Q000494:pharmacology; D054407:Chemokine CCL4; D018925:Chemokines / Q000096:biosynthesis; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000378:metabolism / Q000821:virology; D004854:Herpesvirus 4, Human / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D007107:Immune System / Q000821:virology; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000821:virology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic; D014763:Viral Matrix Proteins / Q000276:immunology
D000914:Antibodies, Viral; D054407:Chemokine CCL4; D018925:Chemokines; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D014763:Viral Matrix Proteins