Pleskoff O, Tréboute C, Alizon M
INSERM U.332, Institut Cochin de Génétique Moléculaire, 75014 Paris, France.
J Virol. 1998 Aug;72(8):6389-97. doi: 10.1128/JVI.72.8.6389-6397.1998.
The human cytomegalovirus (CMV) US28 gene encodes a functional CC chemokine receptor. However, this activity was observed in cells transfected to express US28 and might not correspond to the actual role of the protein in the CMV life cycle. Expression of US28 allows human immunodeficiency virus type 1 (HIV-1) entry into certain CD4(+) cells and their fusion with cells expressing HIV-1 envelope (Env) proteins. Such properties were initially reported for the cellular chemokine receptors CCR5 and CXCR4, which behave as CD4-associated HIV-1 coreceptors. We found that coexpression of US28 and either CXCR4 or CCR5 in CD4(+) cells resulted in enhanced synctium formation with HIV-1 Env+ cells. This positive effect of US28 on cell fusion seems to be distinct from its HIV-1 coreceptor activity. Indeed, enhancement of cell fusion was also observed when US28 was expressed on the HIV-1 Env+ cells instead of an CD4(+) target cells. Furthermore, US28 could enhance cell fusion mediated by other viral proteins, in particular, the G protein of vesicular stomatitis virus (VSV-G). The HIV-1 coreceptor and fusion-enhancing activities could be affected by mutations in different domains of US28. The fusion-enhancing activity of US28 seems to be cell type dependent. Indeed, cells coexpressing VSV-G and US28 fused more efficiently with human, simian, or feline target cells, while US28 had no apparent effect on fusion with the three mouse or rat cell lines tested. The positive effect of US28 on cell fusion might therefore require its interaction with a cell-specific factor. We discuss a possible role for US28 in the fusion of the CMV envelope with target cells and CMV entry.
人巨细胞病毒（CMV）的US28基因编码一种功能性CC趋化因子受体。然而，这种活性是在转染以表达US28的细胞中观察到的，可能并不对应于该蛋白在CMV生命周期中的实际作用。US28的表达使得人类免疫缺陷病毒1型（HIV-1）能够进入某些CD4(+)细胞，并使其与表达HIV-1包膜（Env）蛋白的细胞融合。最初报道细胞趋化因子受体CCR5和CXCR4具有此类特性，它们作为与CD4相关的HIV-1共受体发挥作用。我们发现，在CD4(+)细胞中共表达US28与CXCR4或CCR5，会导致与HIV-1 Env+细胞形成更多的合胞体。US28对细胞融合的这种积极作用似乎与其HIV-1共受体活性不同。实际上，当US28在HIV-1 Env+细胞而非CD4(+)靶细胞上表达时，也观察到了细胞融合的增强。此外，US28可以增强由其他病毒蛋白介导的细胞融合，特别是水疱性口炎病毒（VSV-G）的G蛋白。HIV-1共受体和融合增强活性可能会受到US28不同结构域突变的影响。US28的融合增强活性似乎依赖于细胞类型。的确，共表达VSV-G和US28的细胞与人类、猿猴或猫的靶细胞融合更有效，而US28对所测试的三种小鼠或大鼠细胞系的融合没有明显影响。因此，US28对细胞融合的积极作用可能需要其与细胞特异性因子相互作用。我们讨论了US28在CMV包膜与靶细胞融合及CMV进入过程中可能发挥的作用。
