GB virus C coinfection in advanced HIV type-1 disease is associated with low CCR5 and CXCR4 surface expression on CD4(+) T-cells.
GB virus C coinfection in advanced HIV type-1 disease is associated with low CCR5 and CXCR4 surface expression on CD4(+) T-cells.
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DOI：
10.3851/imp1602
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发表时间：
2010
影响因子：
1.2
通讯作者：
Spengler U
中科院分区：
文献类型：
--
作者：
Schwarze-Zander C;Neibecker M;Othman S;Tural C;Clotet B;Blackard JT;Kupfer B;Luechters G;Chung RT;Rockstroh JK;Spengler U
由于共同的传播途径，在患有人类免疫缺陷病毒（HIV）的患者中，与黄病毒GB病毒C的共感染是常见的。已提出GBV-C共感染对HIV感染产生有益影响。体外研究表明，下调CCR 5是GBV-C调节HIV疾病进展的潜在机制。因此，我们研究了128名HIV患者的CD 4+和CD 8 + T细胞上两种主要HIV辅助受体CCR 5和CXCR 4的表面表达，这些患者根据其GBV-C状态、免疫功能和体内HAART进行分层。应用巢式RT-PCR技术对128例HIV感染者进行了GBV-C感染的检测。使用FACS分析来测量⑶ 4+和⑶ 8 + T细胞上的CCR 5和CXCR 4表面表达。30%（38/128）的患者检测到GBV-C RNA复制。在晚期免疫缺陷的HIV患者中，我们发现CD 4 + T细胞表面CCR 5表达上调。然而，在GBV-C合并感染的患者中，未检测到CCR 5 CD 4 + T细胞的上调。此外，在GBV-C共感染患者中，CXCR 4表面表达降低。这些发现与HAART和HIV病毒载量无关。在GBV-C合并感染的患者中，CD 8 + T细胞上的HIV共受体表达没有改变。因此，HIV疾病中的GBV-C共感染导致免疫缺陷晚期患者的CD 4 + T细胞上两种主要HIV共受体CCR 5和CXCR 4的表达降低，这为GBV-C共感染在晚期HIV疾病中的临床益处提供了可能的分子解释。
Co-infection with the flavivirus GB virus C is frequent in patients suffering from human immunodeficiency virus (HIV) due to shared routes of transmission. GBV-C co-infection has been proposed to exert a beneficial influence on HIV infection. In vitro studies demonstrated down-regulation of CCR5 as a potential mechanism of GBV-C to modulate HIV disease progression. We therefore studied surface expression of the two major HIV co-receptors, CCR5 and CXCR4, on CD4+ and CD8+ T-cells in 128 HIV patients stratified with respect to their GBV-C status, immune function and HAART in vivo. GBV-C infection was studied in 128 HIV patients by nested RT-PCR. FACS analysis was used to measure CCR5 and CXCR4 surface expression on CD4+ and CD8+ T cells. GBV-C RNA replication was detected in 30% (38/128) of patients. In HIV patients with advanced immunodeficiency, we found up-regulation of CCR5 surface expression on CD4+ T cells. However, in patients with GBV-C co-infection, no up-regulation of CCR5 CD4+ T cells was detected. Furthermore, CXCR4 surface expression was reduced in GBV-C co-infected patients. These findings were independent of HAART and HIV viral load. HIV co-receptor expression on CD8+ T cells was not altered in patients with GBV-C co-infection. Thus, GBV-C co-infection in HIV disease leads to reduced expression of the two major HIV co-receptors, CCR5 and CXCR4, on CD4+ T cells in patients with advanced stage of immunodeficiency providing a possible molecular explanation for the clinical benefit of GBV-C co-infection in late stage HIV disease.