本研究旨在探讨HCV和HIV合并感染对肝纤维化的影响。建立了一个共培养系统来积极复制两种病毒,掺入CD4T淋巴细胞(Jurkat),肝星状细胞(LX-2),和肝细胞(Huh7.5)。通过测量HIV受体表达来评估LX-2细胞对HIV感染的易感性,接触无细胞病毒,以及与HIV感染的Jurkat细胞的细胞间接触。这项研究评估了纤维化参数,包括程序性细胞死亡,ROS失衡,细胞因子(IL-6,TGF-β,和TNF-α),和细胞外基质成分(胶原蛋白,α-SMA,和MMP-9)。使用从HCV感染的肝细胞释放的可溶性因子检查HCV感染对LX-2/HIV-Jurkat的影响。尽管LX-2细胞不容易直接感染HIV,观察到旁观者效应,导致氧化应激增加和促纤维化细胞因子释放失调。与HIV感染的Jurkat细胞共培养会加剧肝纤维化,氧化还原不平衡,促纤维化细胞因子的表达,和细胞外基质的生产。相反,HCV感染的Huh7.5细胞表现出升高的促纤维化基因转录,但对LX-2/HIV-Jurkat共培养没有可测量的影响。这项研究强调了HIV感染的淋巴细胞在HCV/HIV合并感染期间如何恶化肝纤维化。它们会增加氧化应激,促纤维化细胞因子水平,通过直接接触和可溶性因子在肝星状细胞中产生细胞外基质。这些见解为合并感染的个体提供了有价值的潜在疗法。
This study aims to explore the influence of coinfection with HCV and HIV on hepatic fibrosis. A coculture system was set up to actively replicate both viruses, incorporating CD4 T lymphocytes (Jurkat), hepatic stellate cells (LX-2), and hepatocytes (Huh7.5). LX-2 cells\' susceptibility to HIV infection was assessed through measurements of HIV receptor expression, exposure to cell-free virus, and cell-to-cell contact with HIV-infected Jurkat cells. The study evaluated profibrotic parameters, including programed cell death, ROS imbalance, cytokines (IL-6, TGF-β, and TNF-α), and extracellular matrix components (collagen, α-SMA, and MMP-9). The impact of HCV infection on LX-2/HIV-Jurkat was examined using soluble factors released from HCV-infected hepatocytes. Despite LX-2 cells being nonsusceptible to direct HIV infection, bystander effects were observed, leading to increased oxidative stress and dysregulated profibrotic cytokine release. Coculture with HIV-infected Jurkat cells intensified hepatic fibrosis, redox imbalance, expression of profibrotic cytokines, and extracellular matrix production. Conversely, HCV-infected Huh7.5 cells exhibited elevated profibrotic gene transcriptions but without measurable effects on the LX-2/HIV-Jurkat coculture. This study highlights how HIV-infected lymphocytes worsen hepatic fibrosis during HCV/HIV coinfection. They increase oxidative stress, profibrotic cytokine levels, and extracellular matrix production in hepatic stellate cells through direct contact and soluble factors. These insights offer valuable potential therapies for coinfected individuals.