Blood, 1 March 2002, Vol. 99, No. 5, pp. 1512-1516
CHEMOKINES
Inhibition of macrophage inflammatory protein-1
production by Epstein-Barr virus
Wolfram J. Jabs,
Hans J. Wagner,
Susanne Maurmann,
Holger Hennig, and
Burkhard Kreft
From the First Department of Medicine and Institute of
Immunology and Transfusion Medicine, University of Lübeck School
of Medicine, Lübeck, Germany; and the Center for Gene and Cell
Therapy, Baylor College of Medicine, Houston, TX.
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
(MIP-1) 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 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 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 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 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.
