Hepatitis C and human immunodeficiency virus envelope proteins cooperatively induce hepatocytic apoptosis via an innocent bystander mechanism
Hepatitis C and human immunodeficiency virus envelope proteins cooperatively induce hepatocytic apoptosis via an innocent bystander mechanism
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DOI：
10.1086/378643
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发表时间：
2003-10-15
影响因子：
6.4
通讯作者：
Groopman, JE
中科院分区：
文献类型：
--
作者：
Munshi, N;Balasubramanian, A;Groopman, JE
我们假设，暴露于丙型肝炎病毒（HCV）和人类免疫缺陷病毒（HIV）的肝细胞可能会受到伤害，通过“无辜的旁观者”的机制，由于病毒蛋白的细胞表面结合。为了评估这一点，我们研究了HCV包膜蛋白E2和T嗜性HIV包膜糖蛋白gp 120对肝细胞的影响，并观察到了有效的细胞凋亡。单独的病毒蛋白质不诱导这种作用。HCV E2和M-嗜性HIV gp 120也诱导显著的凋亡。阻断CXCR 4受体导致细胞凋亡减少。HCV E2和HIV gp 120协同作用触发一组特定的下游信号传导事件，包括上调Fas配体和抗凋亡分子AKT的去磷酸化。这些结果表明，肝损伤可能会发生在HCV/HIV共感染，通过诱导新的下游信号通路，并提供了一个合理的治疗干预，干扰特定的受体和信号分子。
We hypothesized that hepatocytes exposed to hepatitis C virus (HCV) and human immunodeficiency virus (HIV) might be injured via an "innocent bystander" mechanism due to cell-surface binding of viral proteins. To assess this, we studied the effects of HCV envelope protein E2 and T-tropic HIV envelope glycoprotein gp120 on hepatocytes and saw potent apoptosis. Either viral protein alone did not induce this effect. HCV E2 and M-tropic HIV gp120 also induced significant apoptosis. Blocking the CXCR4 receptor led to a reduction in apoptosis. HCV E2 and HIV gp120 acted collaboratively to trigger a specific set of downstream signaling events, including up-regulation of the Fas ligand and dephosphorylation of the anti-apoptotic molecule AKT. These results suggest that hepatic injury may occur in HCV/HIV coinfection through the induction of novel downstream signaling pathways and provide a rationale for therapeutic interventions that interfere with specific receptors and signaling molecules.