Differences in viral dynamics between genotypes 1 and 2 of hepatitis C virus
Differences in viral dynamics between genotypes 1 and 2 of hepatitis C virus
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DOI：
10.1086/315661
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发表时间：
2000-07-01
影响因子：
6.4
通讯作者：
Layden, TJ
中科院分区：
文献类型：
--
作者：
Neumann, AU;Lam, NP;Layden, TJ
许多研究表明，感染丙型肝炎病毒（HCV）的基因型2的患者比基因型1的患者对干扰素（IFN）-α治疗有更好的反应;然而，造成这种差异的机制尚不清楚。在这项研究中，在高剂量IFN诱导治疗期间，比较了基因型之间的病毒动力学，每组患者接受10 MU IFN-α 2b治疗14天，并经常测定HCV RNA水平。分别对每个患者和使用混合效应方法的病毒动力学数据进行非线性拟合，以建立IFN对HCV感染影响的数学模型。IFN在阻断病毒产生方面的抗病毒有效性、游离病毒粒子清除率和HCV感染细胞死亡率对于基因型2患者均显著高于基因型1患者。因此，感染HCV基因型2的患者的更好应答率是多因素的，这是首次发现相同病毒亚型之间的病毒动力学差异，并证明了亚型特异性病毒-宿主-药物相互作用的重要性。
Many studies have shown that patients infected with hepatitis C virus (HCV) of genotype 2 have better response to interferon (IFN)-alpha treatment than genotype 1 patients; however, the mechanisms responsible for this difference are not understood. In this study, viral dynamics during high-dose IFN induction treatment were compared between the genotypes, Patients in each group received 10 MU of IFN-alpha 2b for 14 days, and HCV RNA levels were frequently determined. Nonlinear fitting, both individually for each patient and using a mixed-effects approach, of the viral kinetic data to a mathematical model of the IFN effect on HCV infection was performed, The antiviral effectiveness of IFN in blocking virus production, the free virion clearance rate, and the HCV-infected cell death rate were all significantly higher for genotype 2 patients than for genotype 1 patients. Thus, the better response rate of patients infected with HCV genotype 2 is multifactorial, This is the first finding of a difference in viral dynamics between subtypes of the same virus and demonstrates the importance of subtype-specific virus-host-drug interactions.