Laskus Tomasz, Radkowski Marek, Jablonska Joanna, Kibler Karen, Wilkinson Jeffrey, Adair Debra, Rakela Jorge
Department of Medicine, Mayo Clinic Scottsdale, AZ 85259, USA.
Blood. 2004 May 15;103(10):3854-9. doi: 10.1182/blood-2003-08-2923. Epub 2004 Jan 22.
Hepatitis C virus (HCV) was found to replicate in monocytes/macrophages particularly in patients with human immunodeficiency virus type 1 (HIV-1) infection. This study was undertaken to determine whether HIV facilitates HCV infection of native human macrophages in vitro. Monocytes/macrophages were collected from healthy donors, infected with HIV M-tropic molecular clone, and then exposed to HCV-positive sera. Presence of positive and negative HCV RNA strands was determined with a novel strand-specific quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). Preceding as well as near-simultaneous infection with HIV made the macrophages more susceptible to infection with HCV; in particular, an HCV RNA-negative strand was detectable almost exclusively in the setting of concomitant HIV infection. Furthermore, HCV RNA load correlated with HIV replication level in the early stage of infection. The ratio of positive to negative strand in macrophages was lower than in control liver samples. HIV infection was also found to facilitate HCV replication in a Daudi B-cell line with engineered CD4 expression. It seems that HIV infection can facilitate replication of HCV in monocytes/macrophages either by rendering cells more susceptible to HCV infection or by increasing HCV replication. This could explain the presence of extrahepatic HCV replication in HIV-coinfected individuals.
丙型肝炎病毒(HCV)被发现可在单核细胞/巨噬细胞中复制,尤其是在1型人类免疫缺陷病毒(HIV-1)感染的患者中。本研究旨在确定HIV在体外是否促进天然人类巨噬细胞感染HCV。从健康供体收集单核细胞/巨噬细胞,用HIV M嗜性分子克隆感染,然后暴露于HCV阳性血清。用一种新型的链特异性定量实时逆转录聚合酶链反应(RT-PCR)测定HCV正负RNA链的存在情况。HIV的先感染以及几乎同时感染使巨噬细胞更容易感染HCV;特别是,几乎仅在同时感染HIV的情况下可检测到HCV RNA负链。此外,在感染早期,HCV RNA载量与HIV复制水平相关。巨噬细胞中正负链的比例低于对照肝脏样本。还发现HIV感染可促进HCV在具有工程化CD4表达的Daudi B细胞系中的复制。看来HIV感染可能通过使细胞更容易感染HCV或通过增加HCV复制来促进HCV在单核细胞/巨噬细胞中的复制。这可以解释HIV合并感染个体中肝外HCV复制的存在。