慢性乙肝病毒感染时病毒子半衰期与病毒血症水平显著相关

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慢性乙肝病毒感染时病毒子半衰期与病毒血症水平显著相关
2008-9-24



　　采用数学模型分析乙肝病毒动力学可能有助于揭示HBV感染和宿主应答机制新的方面。为了确定在慢性感染的不同阶段患者血液中病毒子衰退的动力学，我们对定量分析病毒血症和肝内 HBV复制（HBV数量和cccDNA）的实时PCR检测进行数学建模。80例未治的慢性活动性携带者（38例HBeAg阳性，42例HBeAg阴性）入组研究。我们发现循环中的病毒子半衰期非常快（在HBeAg阳性和阴性患者中，中位期分别为46和2.5分钟），并与病毒血症显著相关，当病毒载量下降时，清除率限制加快。为了调查免疫成分是否影响病毒子衰退的动力学，我们在免疫缺陷的尿激酶型血纤维蛋白溶酶原激活子嵌合体小鼠中分析了病毒动力学。小鼠的病毒子半衰期（范围44分钟至>4小时）与高病毒血症的预计值相似，显示这些患者的清除率主要由通常的非特异性机制决定。特别地，小鼠病毒子半衰期与病毒血症无关显示免疫成分在低滴度个体中可显著加速病毒子清除率。

　　结论：我们的分析提示宿主防御机制合循环病毒子水平都影响慢性携带者血清HBV衰退的动力学。确认影响清除率的因素对于将来的抗病毒药物开发非常重要，可能有助于深入研究与其他慢性感染清除相关的机制，如HIV和HCV感染。

Hepatology. 2008 Aug 11. [Epub ahead of print]

Virion half-life in chronic hepatitis B infection is strongly correlated with levels of viremia.

Dandri M, Murray JM, Lutgehetmann M, Volz T, Lohse AW, Petersen J.

Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Analysis of hepatitis B virus (HBV) kinetics with mathematical models may disclose new aspects of HBV infection and host response mechanisms. To determine the kinetics of virion decay from the blood of patients in different phases of chronic infection, we applied mathematical modeling to real-time polymerase chain reaction assays, which enable quantification of viremia and intrahepatic HBV productivity by measuring both copy number and activity of covalently closed circular DNA (relaxed circular DNA/covalently closed circular DNA) in the liver of 80 untreated chronically active HBV carriers (38 hepatitis B e antigen [HBeAg]-positive and 42 HBeAg-negative individuals). We found that the half-life of circulating virions is very fast (median 46 and 2.5 minutes in HBeAg-positive and HBeAg-negative individuals, respectively) and strongly related to viremia, with clearance rates significantly accelerating as viral loads decrease. To investigate whether immune components can influence the kinetics of virion decay, we analyzed viral dynamics in immunodeficient urokinase-type plasminogen activator chimera mice. Virion half-life in mice (range, 44 minutes to >4 hours) was comparable to estimates determined in high viremic carriers, implying that clearance rates in these patients are mostly determined by common nonspecific mechanisms. Notably, the lack of correlation between virion half-life and viremia in mice indicated that immune components significantly accelerate virion clearance rates in individuals with low titers. Conclusion: Our analyses suggest that both host defense mechanisms and levels of circulating virions affect the kinetics of HBV decay assessed in the serum of chronic carriers. Identification of the factors affecting clearance rates will be important for future antiviral drug developments and it may give insights into the mechanisms involved in clearance of other chronic infections, such as human immunodeficiency virus and hepatitis C virus.

宁静温泉

有一个和这篇论文无关的问题：既然病毒半衰期那么短，为什么我们抽取的血液可以放置比较长的时间再检测病毒含量？是谁在清除这些病毒？