Human serum facilitates hepatitis C virus infection, and neutralizing responses inversely correlate with viral replication kinetics at the acute phase of hepatitis C virus infection
Human serum facilitates hepatitis C virus infection, and neutralizing responses inversely correlate with viral replication kinetics at the acute phase of hepatitis C virus infection
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DOI：
10.1128/jvi.79.10.6023-6034.2005
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发表时间：
2005-05-01
影响因子：
5.4
通讯作者：
Cosset, FL
中科院分区：
文献类型：
--
作者：
Lavillette, D;Morice, Y;Cosset, FL
导致丙型肝炎病毒（HCV）自发清除或病毒持续存在的因素是难以捉摸的。了解病毒-宿主相互作用，使急性HCV清除的关键是更有效的治疗和预防策略的发展。在这里，使用一个敏感的中和试验的基础上传染性HCV假颗粒（HCVpp），我们研究了一个血液透析中心在一个单一的医院爆发感染的急性期患者队列的体液免疫反应的动力学。在做出治疗决定之前，对17名患者的HCV感染自发结局进行了6个月的监测。经常采集血液样本（每例患者15 +/- 4）。对主要病毒的系统发育分析显示，只有两种基因型1b毒株中的一种感染。虽然所有患者血清转化，他们的血清诱导两个相反的效果在HCVpp感染检测：抑制和促进。此外，血清促进或抑制感染的能力与感染HCV毒株的存在相关，并将患者分为两组。在第1组中，相对较强的中和反应的逐渐出现与高初始病毒血症的波动性降低相关，导致病毒复制得到控制。第2组患者在急性期内未能减少病毒血症，尽管血清转化，但未检测到中和反应。引人注目的是，第2组的血清，以及幼稚血清，促进感染HCVpp展示HCV糖蛋白从不同的基因型和菌株，包括那些从患者中检索。这些结果提供了新的见解，病毒的持久性和免疫控制的病毒血症的机制。
The factors leading to spontaneous clearance of hepatitis C virus (HCV) or to viral persistence are elusive. Understanding virus-host interactions that enable acute HCV clearance is key to the development of more effective therapeutic and prophylactic strategies. Here, using a sensitive neutralization assay based on infectious HCV pseudoparticles (HCVpp), we have studied the kinetics of humorall responses in a cohort of acute-phase patients infected during a single nosocomial outbreak in a hemodialysis center. The 17 patients were monitored for the spontaneous outcome of HCV infection for 6 months before a treatment decision was made. Blood samples were taken frequently (15 +/- 4 per patient). Phylogenetic analysis of the predominant virus(es) revealed infection by only one of two genotype 1b strains. While all patients seroconverted, their sera induced two opposing effects in HCVpp infection assays: inhibition and facilitation. Furthermore, the ability of sera to facilitate or inhibit infection correlated with the presence of either infecting HCV strain and divided the patients into two groups. In group 1, the progressive emergence of a relatively strong neutralizing response correlated with a fluctuating decrease in high initial viremia, leading to control of viral replication. Patients in group 2 failed to reduce viremia within the acute phase, and no neutralizing responses were detected despite seroconversion. Strikingly, sera of group 2, as well as naive sera, facilitated infection by HCVpp displaying HCV glycoproteins from different genotypes and strains, including those retrieved from patients. These results provide new insights into the mechanisms of viral persistence and immune control of viremia.