Human herpesvirus 7 (HHV-7) is a member of the subfamily Betaherpesvirinae that exhibits a restricted cell tropism, preferentially infecting CD4+ T cells in vitro. HHV-7 encodes two functional chemokine receptors, U12 and U51. The human chemokines that act as ligands for these receptors have been identified as CCL22 (the natural ligand for CCR4) and CCL19 (the natural ligand for CCR7). It was found that murine L1.2 cells co-expressing CCR4 or CCR7 and U12 responded to both CCL22 and CCL19 in calcium-mobilization assays, but migrated in response only to the appropriate ligand for the expressed cellular receptor. Similar results were obtained with L1.2 cells co-expressing CCR4 or CCR7 with U51. These results suggest that the HHV-7 U12 and U51 receptors can function in concert with CCR4 and CCR7 in host-cell signalling pathways.