Regulation of CC chemokine receptor 5 in hepatitis G virus infection
Regulation of CC chemokine receptor 5 in hepatitis G virus infection
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DOI：
10.1097/00002030-200307040-00006
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发表时间：
2003-07-04
期刊：
影响因子：
3.8
通讯作者：
Spengler, U
中科院分区：
文献类型：
--
作者：
Nattermann, J;Nischalke, HD;Spengler, U
简介：流行病学数据表明庚型肝炎病毒（HGV）合并感染与HIV阳性个体生存率提高之间存在关联。然而，HGV影响HIV疾病进展的机制仍不清楚。由于CC趋化因子受体5（CCR5）的下调延迟HIV的进展，我们调查了CCR5的表达是否被改变的淋巴细胞暴露于HGV proteins.Methods：CCR5的表达进行了横断面分析的CD4和CD8 T淋巴细胞的11 HGV阳性和12 HGV阴性的人，谁是纯合子的CCR5野生型基因。通过流式细胞术分析HGV 1：2蛋白与CD81的结合。用固定化HGV E2，抗CD81或HGV感染者的血清蛋白刺激淋巴细胞，并测定CCR5表达和CC趋化因子分泌的变化。结果：我们证明HGV包膜蛋白E2特异性结合T淋巴细胞上的CD81。这种相互作用诱导RANTES的剂量依赖性释放和CCR5表面表达的下调，伴随着CCR5蛋白的细胞内积累。当淋巴细胞与来自HGV感染受试者的血清蛋白孵育时，HGV E2对CCR5表达的这种作用得到证实。结论：HGV E2与CD81相互作用导致RANTES分泌增加和CCR5表面表达降低，HGV感染者CD4和CD8淋巴细胞表面CCR5表达分别降低53%和36%（P < 0.01）。这一机制可能有助于HGV合并感染患者的HIV感染进展延迟。(C)2003年利平科特威廉姆斯威尔金斯。
Introduction: Epidemiological data demonstrate an association between hepatitis G virus (HGV) co-infection and improved survival of HIV-positive individuals. However, the mechanism by which HGV affects progression of HIV disease remains unclear. As down-regulation of CC chemokine receptor 5 (CCR5) delays HIV progression, we investigated whether CCR5 expression is altered by exposure of lymphocytes to HGV proteins.Methods: A cross-sectional analysis of CCR5 expression was carried out on CD4 and CD8 T lymphocytes of 11 HGV-positive and 12 HGV-negative persons, who were homozygous for the CCR5 wild-type gene. Binding of the HGV 1:2 protein to CD81 was analysed by flow cytometry. Lymphocytes were stimulated with immobilized HGV E2, anti-CD81 or serum proteins from HGV-infected subjects and changes in CCR5 expression and CC chemokine secretion were determined.Results: We demonstrate that the HGV envelope protein E2 specifically binds to CD81 on T lymphocytes. This interaction induces a dose-dependent release of RANTES and down-regulation of CCR5 surface expression with concomitant intracellular accumulation of CCR5 proteins. This effect of HGV E2 on CCR5 expression was confirmed when lymphocytes were incubated with serum proteins from HGV-infected subjects. Finally, our cross-sectional analysis revealed CCR5 expression to be reduced by 53% and 36% on CD4 and CD8 lymphocytes of HGV-infected subjects, respectively (P < 0.01).Conclusions: Our results demonstrate that an interaction of HGV E2 with CD81 leads to increased RANTES secretion and decreased CCR5 surface expression. This mechanism might contribute to the delayed progression of HIV-infection in HGV-coinfected patients. (C) 2003 Lippincott Williams Wilkins.