Liver fibrosis is the excessive accumulation of extracellular matrix proteins, primarily collagen, in response to liver injury caused by chronic liver diseases. HIV infection accelerates the progression of liver fibrosis in patients co-infected with HCV or HBV compared to those who are only mono-infected. The early event in the progression of liver fibrosis involves the activation of hepatic stellate cells (HSCs), which entails the loss of lipid droplets (LD) to fuel the production of extracellular matrix components crucial for liver tissue healing. Thus, we are examining the mechanism by which HIV stimulates the progression of liver fibrosis. HIV-R5 tropic infection was unable to induce the expression of TGF-β, collagen deposition, α-smooth muscle actin (α-SMA), and cellular proliferation. However, this infection induced the secretion of the profibrogenic cytokine IL-6 and the loss of LD. This process involved the participation of peroxisome proliferator-activated receptor (PPAR)-α and an increase in lysosomal acid lipase (LAL), along with the involvement of Microtubule-associated protein 1 A/1B-light chain 3 (LC3), strongly suggesting that LD loss could occur through acid lipolysis. These phenomena were mimicked by the gp120 protein from the R5 tropic strain of HIV. Preincubation of HSCs with the CCR5 receptor antagonist, TAK-779, blocked gp120 activity. Additionally, experiments performed with pseudotyped-HIV revealed that HIV replication could also contribute to LD loss. These results demonstrate that the cross-talk between HSCs and HIV involves a series of interactions that help explain some of the mechanisms involved in the exacerbation of liver damage observed in co-infected individuals.

中文翻译：

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HIV 和 gp120 诱导的肝星状细胞脂滴损失导致促纤维化

肝纤维化是细胞外基质蛋白（主要是胶原蛋白）的过度积累，以应对慢性肝病引起的肝损伤。与仅单一感染的患者相比，HIV 感染会加速同时感染 HCV 或 HBV 的患者肝纤维化的进展。肝纤维化进展的早期事件涉及肝星状细胞 (HSC) 的激活，这会导致脂滴 (LD) 的损失，以促进细胞外基质成分的产生，这对肝组织愈合至关重要。因此，我们正在研究艾滋病毒刺激肝纤维化进展的机制。HIV-R5 热带感染不能诱导 TGF-β 的表达、胶原沉积、α-平滑肌肌动蛋白 (α-SMA) 和细胞增殖。然而，这种感染诱导了促纤维化细胞因子 IL-6 的分泌和 LD 的丧失。这一过程涉及过氧化物酶体增殖物激活受体 (PPAR)-α 的参与和溶酶体酸性脂肪酶 (LAL) 的增加，以及微管相关蛋白 1 A/1B-轻链 3 (LC3) 的参与，强烈表明LD 损失可能是通过酸性脂肪分解发生的。HIV R5 热带毒株的 gp120 蛋白模仿了这些现象。HSC 与 CCR5 受体拮抗剂 TAK-779 预孵育可阻断 gp120 活性。此外，用假型 HIV 进行的实验表明，HIV 复制也可能导致 LD 丢失。这些结果表明，HSC 和 HIV 之间的串扰涉及一系列相互作用，这些相互作用有助于解释在共同感染个体中观察到的肝损伤加剧的一些机制。