Milne R S, Mattick C, Nicholson L, Devaraj P, Alcami A, Gompels U A
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine and Kings's College School of Medicine and Dentistry, University of London, United Kingdom.
J Immunol. 2000 Mar 1;164(5):2396-404. doi: 10.4049/jimmunol.164.5.2396.
The human herpesvirus 6 (HHV-6) U51 gene defines a new family of betaherpesvirus-specific genes encoding multiple transmembrane glycoproteins with similarity to G protein-coupled receptors, in particular, human chemokine receptors. These are distinct from the HHV-6 U12 and HCMV US28 family. In vitro transcription and translation as well as transient cellular expression of U51 showed properties of a multiple transmembrane protein with a 30-kDa monomer as well as high m.w. aggregates or oligomers. Transient cellularly expressed U51 also appeared to form dimeric intermediates. Despite having only limited sequence similarity to chemokine receptors, U51 stably expressed in cell lines showed specific binding of the CC chemokine RANTES and competitive binding with other beta chemokines, such as eotaxin; monocyte chemoattractant protein 1, 3, and 4; as well as the HHV-8 chemokine vMIPII. In epithelial cells already secreting RANTES, U51 expression resulted in specific transcriptional down-regulation. This correlated with reduced secretion of RANTES protein into the culture supernatants. Regulation of RANTES levels may alter selective recruitment of circulating inflammatory cells that the virus can infect and thus could mediate the systemic spread of the virus from initial sites of infection in epithelia. Alternatively, chemokine regulation could modulate a protective inflammatory response to aid the spread of virus by immune evasion. Such mimicry, by viral proteins, of host receptors leading to down-regulation of chemokine expression is a novel immunomodulatory mechanism.
人类疱疹病毒6型（HHV - 6）的U51基因定义了一个新的β疱疹病毒特异性基因家族，该家族编码多种跨膜糖蛋白，这些糖蛋白与G蛋白偶联受体，特别是人类趋化因子受体具有相似性。它们与HHV - 6的U12和人巨细胞病毒（HCMV）的US28家族不同。U51的体外转录和翻译以及在细胞中的瞬时表达显示出一种多跨膜蛋白的特性，其单体为30 kDa，还有高分子量的聚集体或寡聚体。在细胞中瞬时表达的U51似乎也形成二聚体中间体。尽管与趋化因子受体只有有限的序列相似性，但在细胞系中稳定表达的U51显示出对CC趋化因子RANTES的特异性结合以及与其他β趋化因子的竞争性结合，如嗜酸性粒细胞趋化因子；单核细胞趋化蛋白1、3和4；以及HHV - 8趋化因子vMIPII。在已经分泌RANTES的上皮细胞中，U51的表达导致特异性转录下调。这与RANTES蛋白分泌到培养上清液中的减少相关。RANTES水平的调节可能会改变病毒能够感染的循环炎症细胞的选择性募集，从而可能介导病毒从上皮细胞的初始感染部位进行全身扩散。或者，趋化因子调节可以调节保护性炎症反应，以通过免疫逃避帮助病毒传播。病毒蛋白对宿主受体的这种模拟导致趋化因子表达下调是一种新的免疫调节机制。
