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Journal of Virology, July 2003, p. 7393-7400, Vol. 77, No. 13
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.13.7393-7400.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The Virus-Encoded Chemokine vMIP-II Inhibits Virus-Induced Tc1-Driven Inflammation

Morten Lindow,1,{dagger} Anneline Nansen,2,{ddagger} Christina Bartholdy,2 Annette Stryhn,2,{ddagger} Nils J. V. Hansen,2,§ Thomas P. Boesen,1,|| Timothy N. C. Wells,3 Thue W. Schwartz,1 and Allan R. Thomsen2*

Laboratory for Molecular Pharmacology,1 Institute of Medical Microbiology and Immunology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark,2 Serono International SA, Geneva, Switzerland3

Received 24 January 2003/ Accepted 8 April 2003

The human herpesvirus 8-encoded protein vMIP-II is a potent in vitro antagonist of many chemokine receptors believed to be associated with attraction of T cells with a type 1 cytokine profile. For the present report we have studied the in vivo potential of this viral chemokine antagonist to inhibit virus-induced T-cell-mediated inflammation. This was done by use of the well-established model system murine lymphocytic choriomeningitis virus infection. Mice were infected in the footpad, and the induced CD8+ T-cell-dependent inflammation was evaluated in mice subjected to treatment with vMIP-II. We found that inflammation was markedly inhibited in mice treated during the efferent phase of the antiviral immune response. In vitro studies revealed that vMIP-II inhibited chemokine-induced migration of activated CD8+ T cells, but not T-cell-target cell contact, granule exocytosis, or cytokine release. Consistent with these in vitro findings treatment with vMIP-II inhibited the adoptive transfer of a virus-specific delayed-type hypersensitivity response in vivo, but only when antigen-primed donor cells were transferred via the intravenous route and required to migrate actively, not when the cells were injected directly into the test site. In contrast to the marked inhibition of the effector phase, the presence of vMIP-II during the afferent phase of the immune response did not result in significant suppression of virus-induced inflammation. Taken together, these results indicate that chemokine-induced signals are pivotal in directing antiviral effector cells toward virus-infected organ sites and that vMIP-II is a potent inhibitor of type 1 T-cell-mediated inflammation.

* Corresponding author. Mailing address: Institute of Medical Microbiology and Immunology, University of Copenhagen, The Panum Institute 22.5.16, 3C Blegdamsvej, DK-2200 Copenhagen N, Denmark. Phone: 45 35 32 78 71. Fax: 45 35 32 78 91. E-mail: A.R.Thomsen{at}immi.ku.dk.

{dagger} Present address: Bioinformatics Centre, University of Copenhagen, Copenhagen, Denmark.

{ddagger} Present address: Statens Serum Institut, Copenhagen, Denmark.

§ Present address: Praecis Pharmaceuticals Inc., Waltham, Mass.

|| Present address: Maxygen A/S, Hørsholm, Denmark.

Journal of Virology, July 2003, p. 7393-7400, Vol. 77, No. 13
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.13.7393-7400.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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