Isegawa Y, Ping Z, Nakano K, Sugimoto N, Yamanishi K
Department of Microbiology, Osaka University Medical School, Suita, Osaka 565, Japan.
J Virol. 1998 Jul;72(7):6104-12. doi: 10.1128/JVI.72.7.6104-6112.1998.
Human herpesvirus 6 (HHV- 6), which belongs to the betaherpesvirus subfamily and infects mainly T cells in vitro, causes acute and latent infections. HHV- 6 contains two genes (U12 and U51) that encode putative homologs of cellular G-protein-coupled receptors (GCR), while three other betaherpesviruses, human cytomegalovirus, murine cytomegalovirus, and human herpesvirus 7, have three, one, and two GCR-homologous genes, respectively. The U12 gene is expressed late in infection from a spliced mRNA. The U12 gene was cloned, and the protein was expressed in cells and analyzed for its biological characteristics. U12 functionally encoded a calcium-mobilizing receptor for beta-chemokines such as regulated upon activation, normal T expressed and secreted (RANTES), macrophage inflammatory proteins 1alpha and 1beta (MIP-1alpha and MIP-1beta) and monocyte chemoattractant protein 1 but not for the alpha-chemokine interleukin-8, suggesting that the chemokine selectivity of the U12 product was distinct from that of the known mammalian chemokine receptors. These findings suggested that the product of U12 may play an important role in the pathogenesis of HHV- 6 through transmembrane signaling by binding with beta-chemokines.
人类疱疹病毒6型（HHV-6）属于β疱疹病毒亚科，在体外主要感染T细胞，可引起急性和潜伏感染。HHV-6含有两个基因（U12和U51），它们编码细胞G蛋白偶联受体（GCR）的假定同源物，而其他三种β疱疹病毒，即人类巨细胞病毒、鼠巨细胞病毒和人类疱疹病毒7型，分别有三个、一个和两个GCR同源基因。U12基因在感染后期从剪接的mRNA表达。U12基因被克隆，其蛋白在细胞中表达并分析其生物学特性。U12在功能上编码一种钙动员受体，可识别β趋化因子，如活化正常T细胞表达和分泌因子（RANTES）、巨噬细胞炎性蛋白1α和1β（MIP-1α和MIP-1β）以及单核细胞趋化蛋白1，但不能识别α趋化因子白细胞介素-8，这表明U12产物的趋化因子选择性与已知的哺乳动物趋化因子受体不同。这些发现表明，U12产物可能通过与β趋化因子结合进行跨膜信号传导，在HHV-6的发病机制中发挥重要作用。
