Human herpesvirus 7 (HHV-7), which belongs to the betaherpesvirus subfamily, infects mainly CD4 � T cells in vitro and infects children during infancy. After the primary infection, HHV-7 becomes latent. 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 gene, we cloned the gene and expressed the U12 protein in cells. The U12 gene encoded a calcium-mobilizing receptor for the EBI1 ligand chemokine-macrophage inflammatory protein 3 � (ELC/MIP-3�) but not for other chemokines, suggesting that the chemokine selectivity of the U12 gene product is distinct from that of the known mammalian chemokine receptors. These studies revealed that U12 activates distinct transmembrane signaling pathways that may mediate biological functions by binding with a �-chemokine, ELC/MIP-3�. Human herpesvirus 7 (HHV-7) was isolated in 1990 from a healthy individual whose cells were stimulated with an antibody against CD3 and then incubated with interleukin-2 (IL-2) (17). HHV-7 is a ubiquitous virus that is similar to HHV-6. The primary infection of HHV-7, like that of HHV-6, causes exanthem subitum or high fever, although the apparent infectio
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