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Journal of Virology, June 2005, p. 7068-7076, Vol. 79, No. 11
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.11.7068-7076.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Human Herpesvirus 7 Open Reading Frames U12 and U51 Encode Functional ß-Chemokine Receptors

Kenjiro Tadagaki, Kazushi Nakano,{dagger} and Koichi Yamanishi*

Department of Microbiology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

Received 3 September 2004/ Accepted 29 December 2004

Human herpesvirus 7 (HHV-7), which belongs to the betaherpesvirus subfamily and infects mainly CD4+ T cells in vitro, infects children during infancy. HHV-7 contains two genes, U12 and U51, that encode putative homologs of cellular G-protein-coupled receptors. To analyze the biological function of the U12 and U51 genes, we cloned these genes and expressed the proteins in cells. U12 and U51 encoded functional calcium-mobilizing receptors for ß-chemokines, which include thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), EBI1-ligand chemokine (ELC), and secondary lymphoid-tissue chemokine (SLC), but not for other chemokines, suggesting that the chemokine selectivities of the U12 and U51 products were distinct from those of the known mammalian chemokine receptors. ELC and SLC induced migration in Jurkat cells stably expressing U12, but TARC and MDC did not. In contrast, none of these chemokines induced migration in Jurkat cells stably expressing U51. Together, these data indicate that the products of U12 and U51 may play important and different roles in the pathogenesis of HHV-7 through transmembrane signaling.

* Corresponding author. Mailing address: Department of Microbiology C1, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. Phone: 81-6-6879-3323. Fax: 81-6-6879-3329. E-mail: yamanisi{at}micro.med.osaka-u.ac.jp.

{dagger} Present address: Molecular Virology Program, Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.

Journal of Virology, June 2005, p. 7068-7076, Vol. 79, No. 11
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.11.7068-7076.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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