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The Journal of Immunology, 2009, 182, 6861 -6869
Copyright © 2009 by The American Association of Immunologists, Inc.
doi:10.4049/jimmunol.0801826

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Chemokine Receptor CCR7 Contributes to a Rapid and Efficient Clearance of Lytic Murine {gamma}-Herpes Virus 68 from the Lung, Whereas Bronchus-Associated Lymphoid Tissue Harbors Virus during Latency1

Jessica R. Kocks*, Heiko Adler{dagger}, Heike Danzer*, Katharina Hoffmann*, Danny Jonigk{ddagger}, Ulrich Lehmann{ddagger} and Reinhold Förster2,*

* Institute of Immunology, Hannover Medical School, Hannover, Germany; {dagger} Institute of Molecular Immunology, Clinical Cooperation Group Hematopoietic Cell Transplantation, Helmholtz Zentrum München-German Research Center for Environmental Health, Munich, Germany; and {ddagger} Institute of Pathology, Hannover Medical School, Hannover, Germany

Murine {gamma}-herpes virus 68 is a natural rodent pathogen closely related to the human {gamma}-herpes viruses Kaposi’s sarcoma-associated herpes virus and EBV. By intranasally infecting wild-type and CCR7-deficient mice, we investigated whether CCR7 is necessary for viral clearance from the lung and the establishment of latency. We found during the lytic phase of infection that inflammation in lungs of CCR7–/– mice was more severe and viral load significantly higher compared with wild-type littermates. In addition, activation of T cells was delayed and clearance of the inflammation was retarded in mutant lungs, demonstrating that CCR7 is necessary for a rapid and efficient immune response. However, for the establishment of splenomegaly and latency, the presence of CCR7 was dispensable. Finally, by microdissecting BALT, we could demonstrate that these ectopic lymphoid structures are a place in the lung where virus resides during latency.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work has been supported by Deutsche Forschungsgemeinschaft Grant SFB587-B3 to R.F. H.A. has been supported by grants from the Deutsche Forschungsgemeinschaft (Ad 121/2-4) and the Bundesministerium fur Bildung, Wissenschaft, Forschung und Technologie (Nationales Genomforschungsnetz plus, Förderkennzeichen 01GS0802).

2 Address correspondence and reprint requests to Dr. Reinhold Förster, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany. E-mail address: foerster.reinhold{at}mh-hannover.de

3 Abbreviations used in this paper: IM, infectious mononucleosis; brLN, bronchial lymph node; DC, dendritic cell; i.n., intranasal; LN, lymph node; LT, lymphotoxin; MHV-68, murine {gamma}-herpes virus 68; ORF, open reading frame; PFA, paraformaldehyde; p.i., postinfection; rpl8, ribosomal protein L8.







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