Hepatitis C virus particles of different density in the blood of chronically infected immunocompetent and immunodeficient patients: Implications for virus clearance by antibody
Hepatitis C virus particles of different density in the blood of chronically infected immunocompetent and immunodeficient patients: Implications for virus clearance by antibody
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慢性感染的免疫功能正常和免疫缺陷患者血液中不同密度的丙型肝炎病毒颗粒：抗体清除病毒的意义
DOI：
10.1002/jmv.10208
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发表时间：
2002
影响因子：
12.7
通讯作者：
G. Toms
中科院分区：
文献类型：
--
作者：
W. Pumeechockchai;D. Bevitt;K. Agarwal;T. Petropoulou;B. Langer;B. Belohradsky;M. Bassendine;G. Toms
本研究的目的是分析体液免疫应答对慢性感染患者血液中含丙型肝炎病毒（HCV）RNA颗粒的产生和清除的影响。血液样品经连续浮选超离心分离后，HCVRNA分为三个部分：低浓度< 1.063 g/ml，中浓度1.063-1.21 g/ml，高浓度> 1.21 g/ml。血清低密度脂蛋白与低密度颗粒共分级，高密度脂蛋白与中密度颗粒共分级。免疫球蛋白仅在高密度级分中发现。在先天性免疫缺陷患者中，没有或低血清抗体的病毒，平均HCV RNA滴度是相等的，在每个部分，在约105 IU/ml。然而，在抗体阳性、免疫功能正常的患者中，大多数患者的低密度组分和高密度组分中的病毒滴度降低或不存在，表明这些组分中的病毒颗粒受到抗体介导的清除。两个患者组中中等密度颗粒的滴度大致相等，表明这些颗粒既不是由体液免疫应答产生的，也不是由体液免疫应答清除的。免疫沉淀实验表明，中等密度的颗粒不与高密度脂蛋白或免疫球蛋白复合。阐明这些颗粒在血液中产生和维持的机制可能会对病毒持续存在的机制提供有价值的见解。医学病毒学杂志68：335-342，2002.© 2002 Wiley利斯公司
The purpose of this study was to analyse the influence of the humoral immune response on the generation and clearance of hepatitis C virus (HCV) RNA containing particles in the blood of chronically infected patients. Blood samples were fractionated by sequential flotation ultracentrifugation and HCV RNA was recovered in three fractions: low density of < 1.063 g/ml, intermediate density of 1.063–1.21 g/ml, and high density of > 1.21 g/ml. Serum low‐density lipoproteins co‐fractionated with the low‐density particles, and high‐density lipoproteins co‐fractionated with the intermediate‐density particles. Immunoglobulins were found exclusively in the high‐density fractions. In patients with congenital immunodeficiencies, with no or low serum antibodies to the virus, mean HCV RNA titres were equal in each fraction, at approximately 105 IU/ml. In antibody‐positive, immunocompetent patients, however, virus titres in the low‐density fraction and those in the high‐density fraction were reduced or absent in most patients, suggesting that virus particles in these fractions are subject to antibody‐mediated clearance. Particles of intermediate density were approximately equal in titre in both patient groups, suggesting that these particles are neither generated by, nor cleared, as a result of the humoral immune response. Immunoprecipitation experiments indicated that particles of intermediate density were not complexed with either high‐density lipoprotein or immunoglobulins. Elucidation of the mechanisms by which these particles are generated and maintained in the blood may provide valuable insight into the mechanism of virus persistence. J. Med. Virol. 68:335–342, 2002. © 2002 Wiley‐Liss, Inc.