Pham Tram N Q, King Dawn, Macparland Sonya A, McGrath Jerry S, Reddy S Bharati, Bursey Ford R, Michalak Tomasz I
Molecular Virology and Hepatology Research, Division of BioMedical Sciences, Memorial University, St. John,s, Newfoundland and Labrador, Canada.
Gastroenterology. 2008 Mar;134(3):812-22. doi: 10.1053/j.gastro.2007.12.011. Epub 2007 Dec 14.
BACKGROUND & AIMS: Infection of the lymphatic system by hepatitis C virus (HCV) appears to be an intrinsic characteristic of chronic hepatitis C (CHC) and low-level (occult) HCV infection, but the subsets of immune cells involved were not defined. The aim of this study was to characterize HCV replication status and to assess virus compartmentalization in CD4+ and CD8+ T lymphocytes, B cells, and monocytes in CHC, and silent infection persisting after resolution of hepatitis C.
Immune cell subtypes isolated from 7 patients with CHC and 7 individuals with occult infection were analyzed for HCV-RNA-positive and -negative strands and, in selected cases, nonstructural protein 5A display and HCV variants.
All subtypes of immune cells investigated support HCV replication in both forms of infection, although significant differences were found between patients, and virus loads in the cells were greater in CHC than in occult infection. Although HCV RNA occurred at a comparable frequency in all cell subtypes in CHC, monocytes contained the greatest loads. In contrast, B cells tended to carry the highest virus quantities in occult infection, whereas monocytes appeared to be the least frequently infected. Detection of HCV nonstructural protein 5A and HCV variants that were not found in plasma confirmed virus replication in different immune cell types.
This work documents that the immune system supports HCV replication regardless of clinical appearance of infection and identifies immune cells that are reservoirs of HCV in symptomatic and occult infections.
丙型肝炎病毒（HCV）感染淋巴系统似乎是慢性丙型肝炎（CHC）和低水平（隐匿性）HCV感染的一个内在特征，但其中涉及的免疫细胞亚群尚未明确。本研究的目的是明确CHC中HCV的复制状态，并评估CD4⁺和CD8⁺T淋巴细胞、B细胞及单核细胞中病毒的分隔情况，以及丙型肝炎消退后持续存在的隐匿性感染情况。
对从7例CHC患者和7例隐匿性感染个体中分离出的免疫细胞亚型进行分析，检测HCV - RNA阳性和阴性链，并在选定病例中检测非结构蛋白5A的表达及HCV变异体。
在两种感染形式中，所有研究的免疫细胞亚型均支持HCV复制，尽管患者之间存在显著差异，且CHC患者细胞中的病毒载量高于隐匿性感染患者。虽然CHC患者所有细胞亚型中HCV RNA出现的频率相当，但单核细胞中的病毒载量最高。相比之下，隐匿性感染中B细胞携带的病毒量往往最高，而单核细胞似乎是感染频率最低的。在血浆中未发现的HCV非结构蛋白5A和HCV变异体的检测证实了不同免疫细胞类型中的病毒复制。
本研究证明，无论感染的临床表现如何，免疫系统均支持HCV复制，并确定了在有症状和隐匿性感染中作为HCV储存库的免疫细胞。
