This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jensen, K. K. Articles by Lira, S. A. Search for Related Content PubMed PubMed Citation Articles by Jensen, K. K. Articles by Lira, S. A.

Disruption of CCL21-Induced Chemotaxis In Vitro and In Vivo by M3, a Chemokine-Binding Protein Encoded by Murine Gammaherpesvirus 68

Department of Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey 07033,¹ Laboratory for Molecular Pharmacology, Department of Pharmacology, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark,² Faculdade de Medicina de Lisboa, 1649-028 Lisbon,³ Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal,⁴ Departments of Medicine and Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, United Kingdom⁵

Received 24 June 2002/ Accepted 23 September 2002

Chemokine-binding proteins represent a novel class of antichemokine agents encoded by poxviruses and herpesviruses. One such protein is encoded by the M3 gene present in the murine gammaherpesvirus 68 (MHV-68) genome. The M3 gene encodes a secreted 44-kDa protein that binds with high affinity to certain murine and human chemokines and has been shown to block chemokine signaling in vitro. However, there has been no direct evidence that M3 blocks chemokine activity in vivo, nor has the nature of M3-chemokine interaction been defined. To better understand the ability of M3 to block chemokine activity in vivo, we examined its interaction with a specific subset of chemokines expressed in lymphoid tissues, areas where gammaherpesviruses characteristically establish latency. Here we show that M3 blocks in vitro chemotaxis induced by CCL19 and CCL21, chemokines expressed constitutively in secondary lymphoid tissues. Moreover, we provide evidence that chemokine M3 binding exhibits positive cooperativity. In vivo, the expression of M3 in the pancreas of transgenic mice inhibits recruitment of lymphocytes induced by transgenic expression of CCL21 in this organ. The ability of M3 to block the biological activity of chemokines may represent an important strategy used by MHV-68 to evade immune detection and favor viral replication in the infected host.

This article has been cited by other articles:

• Andreansky, S., Liu, H., Adler, H., Koszinowski, U. H., Efstathiou, S., Doherty, P. C. (2004). The limits of protection by "memory" T cells in Ig-/- mice persistently infected with a {gamma}-herpesvirus. Proc. Natl. Acad. Sci. USA 101: 2017-2022 [Abstract] [Full Text]