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慢性感染患者外周血和肝脏浸润中的单核细胞丙型肝炎病毒感染

Hepatitis C virus infection of mononuclear cells from peripheral blood and liver infiltrates in chronically infected patients.

作者信息

Zignego A L, De Carli M, Monti M, Careccia G, La Villa G, Giannini C, D'Elios M M, Del Prete G, Gentilini P

机构信息

Istitute of Internal Medicine, University of Florence School of Medicine, Italy.

出版信息

J Med Virol. 1995 Sep;47(1):58-64. doi: 10.1002/jmv.1890470112.

DOI:10.1002/jmv.1890470112
PMID:8551260
Abstract

The mechanisms underlying chronicity of hepatitis C virus (HCV) infection are poorly understood, but the importance of impaired viral clearance by the immune system has been suggested. The prevalence of HCV infection of peripheral blood mononuclear cells (PBMC) was in investigated in 34 persistently infected patients with anti-HCV (7 with liver cirrhosis, 10 with chronic active hepatitis, 5 with chronic persistent hepatitis, 4 with chronic lobular hepatitis, and 8 healthy carriers) by polymerase chain reaction (PCR). HCV infection of 116 T cell clones derived from liver infiltrating mononuclear cells obtained from 3 patients with chronic liver disease was examined using the same methods. HCV genomic sequences were found in fresh, unstimulated PBMC from 20 patients with cirrhosis, and chronic active and persistent hepatitis, but in none of the healthy carriers and only in mitogen-activated cells from 1 out of 4 patients with autoresolving chronic lobular hepatitis. Active PBMC infection was confirmed by identification of anti-genomic HCV sequences in the majority of HCV RNA-positive cells (fresh or mitogen-stimulated). A high percentage of T cell clones obtained from liver infiltrates were found to be infected by HCV. These findings suggest that HCV infection of lymphatic cells plays a role in the pathogenesis of chronically evolving liver damage. PBMC may represent a reservoir for latent infection and a site for viral multiplication.

摘要

丙型肝炎病毒(HCV)慢性感染的潜在机制尚不清楚,但免疫系统对病毒清除能力受损的重要性已被提出。通过聚合酶链反应(PCR)对34例抗HCV持续感染患者(7例肝硬化、10例慢性活动性肝炎、5例慢性持续性肝炎、4例慢性小叶性肝炎患者以及8例健康携带者)外周血单个核细胞(PBMC)的HCV感染情况进行了研究。采用相同方法检测了3例慢性肝病患者肝脏浸润单个核细胞来源的116个T细胞克隆的HCV感染情况。在20例肝硬化、慢性活动性肝炎和慢性持续性肝炎患者的新鲜、未刺激的PBMC中发现了HCV基因组序列,但在健康携带者中均未发现,仅在4例自限性慢性小叶性肝炎患者中1例的丝裂原激活细胞中发现。通过在大多数HCV RNA阳性细胞(新鲜或丝裂原刺激的)中鉴定抗基因组HCV序列,证实了PBMC的活跃感染。从肝脏浸润物中获得的高比例T细胞克隆被发现感染了HCV。这些发现表明,淋巴细胞的HCV感染在慢性进展性肝损伤的发病机制中起作用。PBMC可能是潜伏感染的储存库和病毒增殖的场所。

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