Human herpesvirus 6 open reading frame U12 encodes a functional β-chemokine receptor
Human herpesvirus 6 open reading frame U12 encodes a functional β-chemokine receptor
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DOI：
10.1128/jvi.72.7.6104-6112.1998
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发表时间：
1998-07-01
影响因子：
5.4
通讯作者：
Yamanishi, K
中科院分区：
文献类型：
--
作者：
Isegawa, Y;Ping, Z;Yamanishi, K
人疱疹病毒6 （HHV-6）属于乙型疱疹病毒亚家族，在体外主要感染T细胞，可引起急性和潜伏性感染，HHV-6含有两个基因（U12和U51），编码细胞g蛋白偶联受体（GCR）的同源物，而另外三种乙型疱疹病毒，人巨细胞病毒、鼠巨细胞病毒和人疱疹病毒7分别具有三个、一个和两个GCR同源基因。U12基因在感染后期通过剪接的mRNA表达。克隆了U12基因，在细胞中表达了该蛋白，并对其生物学特性进行了分析。U12在功能上编码了β趋化因子的钙动员受体，如激活后调节的正常T表达和分泌（RANTES）、巨噬细胞炎症蛋白1 α和1 β （MIP-1 α和MIP-1 β）和单核细胞趋化蛋白1，但不编码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不同于已知的哺乳动物趋化因子受体。这些发现提示U12的产物可能通过与趋化因子结合的跨膜信号通路在HHV-6的发病过程中发挥重要作用。
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 1 alpha and 1 beta (MIP-1 alpha and MIP-1 beta) 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.