Dichamp Isabelle, Abbas Wasim, Kumar Amit, Di Martino Vincent, Herbein Georges
Pathogens and Inflammation Department, UPRES EA4266, SFR FED 4234, University of Franche-Comté, Besancon, France; Department of Virology, CHRU Besançon, Besançon, France.
Pathogens and Inflammation Department, UPRES EA4266, SFR FED 4234, University of Franche-Comté, Besancon, France; Department of Hepatology, CHRU Besançon, Besançon, France.
PLoS One. 2014 May 8;9(5):e96907. doi: 10.1371/journal.pone.0096907. eCollection 2014.
During HCV infection, the activation status of peripheral blood monocytes and its impact on HCV replication are poorly understood. We hypothesized that a modified activation of peripheral blood monocytes in HIV-HCV coinfected compared to HCV monoinfected patients may contribute to different monocytes reservoirs of HCV replication.
We performed a case-control analysis involving HCV-infected patients with and without HIV coinfection. In peripheral blood mononuclear cells (PBMCs), peripheral blood lymphocytes (PBLs) and peripheral blood monocytes isolated from HCV monoinfected and HIV-HCV coinfected patients, intracellular HCV load and a marker of cellular activation, nuclear factor-kappaB (NF-κB) activation, were quantified using intracellular detection of HCV-core protein and electrophoretic mobility shift assay, respectively.
Intracellular HCV loads were higher in monocytes isolated from HIV-HCV coinfected patients than in those of monoinfected patients. Among PBMCs isolated from HIV-HCV coinfected patients, intracellular HCV loads were higher in monocytes compared to PBLs. Cellular activation as measured by NF-κB activation was higher in monocytes isolated from HIV-HCV coinfected patients than in those of monoinfected patients.
Our results reveal the peripheral blood monocytes as an important extrahepatic reservoir for HCV in HIV-HCV coinfected patients and indicate a potential association between the activation state of monocytes and the size of the HCV reservoir in HIV-HCV coinfected patients.
在丙型肝炎病毒(HCV)感染期间,外周血单核细胞的激活状态及其对HCV复制的影响尚不清楚。我们推测,与单纯HCV感染患者相比,HIV-HCV合并感染患者外周血单核细胞的激活状态改变可能导致HCV复制的单核细胞储存库不同。
我们进行了一项病例对照分析,纳入了HCV感染且合并或未合并HIV感染的患者。分别从单纯HCV感染和HIV-HCV合并感染患者中分离外周血单个核细胞(PBMC)、外周血淋巴细胞(PBL)和外周血单核细胞,采用细胞内检测HCV核心蛋白和电泳迁移率变动分析,分别定量细胞内HCV载量和细胞激活标志物核因子κB(NF-κB)的激活情况。
从HIV-HCV合并感染患者中分离的单核细胞内HCV载量高于单纯感染患者。在从HIV-HCV合并感染患者中分离的PBMC中,单核细胞内的HCV载量高于PBL。通过NF-κB激活检测的细胞激活在从HIV-HCV合并感染患者中分离的单核细胞中高于单纯感染患者。
我们的结果揭示了外周血单核细胞是HIV-HCV合并感染患者中HCV重要的肝外储存库,并表明单核细胞的激活状态与HIV-HCV合并感染患者中HCV储存库大小之间存在潜在关联。