HIV-1 Nef is transferred from expressing T cells to hepatocytic cells through conduits and enhances HCV replication.
HIV-1 Nef is transferred from expressing T cells to hepatocytic cells through conduits and enhances HCV replication.
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HIV-1 NEF通过导管从表达T细胞转移到肝细胞细胞，并增强HCV复制。
DOI：
10.1371/journal.pone.0099545
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
He JJ
中科院分区：
文献类型：
--
作者：
Park IW;Fan Y;Luo X;Ryou MG;Liu J;Green L;He JJ
HIV-1感染促进了丙型肝炎病毒的复制，从而加速了丙型肝炎病毒介导的肝细胞癌。然而，发生这种情况的确切分子机制目前尚不清楚。我们的数据显示，传染性HIV-1未能在人肝细胞系中复制。即使将感染HIV-1前病毒DNA的细胞系与Jurkat T细胞共培养，也没有观察到明显的病毒复制，这表明混合感染患者的肝脏恶化问题不是由于HIV-1在感染丙型肝炎病毒的宿主的肝细胞中复制所致。相反，通过管道将HIV-1Nef蛋白从表达NEF的T细胞转移到肝细胞，当肝细胞与表达NEF的Jurkat细胞共同培养24小时时，高达16%(平均10%)的细胞携带Nef。此外，Nef改变了脂滴(LD)的大小和数量，并持续地将目标亚基因组复制子细胞中的丙型肝炎病毒复制上调1.5∼2.5倍，这与最初缓慢的病毒复制有关。NEF还显著增加了活性氧物种(ROS)的产生，并增强了乙醇介导的对丙型肝炎病毒复制的上调，从而加速了肝癌的发生。综上所述，这些数据表明，HIV-1Nef是通过促进丙型肝炎病毒复制和协调调节细胞内和细胞外关键分子对肝脏腐烂的调节而加速肝脏发病进展的关键因素。
HIV-1 infection enhances HCV replication and as a consequence accelerates HCV-mediated hepatocellular carcinoma (HCC). However, the precise molecular mechanism by which this takes place is currently unknown. Our data showed that infectious HIV-1 failed to replicate in human hepatocytic cell lines. No discernible virus replication was observed, even when the cell lines transfected with HIV-1 proviral DNA were co-cultured with Jurkat T cells, indicating that the problem of liver deterioration in the co-infected patient is not due to the replication of HIV-1 in the hepatocytes of the HCV infected host. Instead, HIV-1 Nef protein was transferred from nef-expressing T cells to hepatocytic cells through conduits, wherein up to 16% (average 10%) of the cells harbored the transferred Nef, when the hepatocytic cells were co-cultured with nef-expressing Jurkat cells for 24 h. Further, Nef altered the size and numbers of lipid droplets (LD), and consistently up-regulated HCV replication by 1.5∼2.5 fold in the target subgenomic replicon cells, which is remarkable in relation to the initially indolent viral replication. Nef also dramatically augmented reactive oxygen species (ROS) production and enhanced ethanol-mediated up-regulation of HCV replication so as to accelerate HCC. Taken together, these data indicate that HIV-1 Nef is a critical element in accelerating progression of liver pathogenesis via enhancing HCV replication and coordinating modulation of key intra- and extra-cellular molecules for liver decay.
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影响因子：
64.5
作者：
AIKEN, C;KONNER, J;TRONO, D
通讯作者：
TRONO, D
DOI：
10.1007/978-1-60761-999-4_19
发表时间：
2011-01-01
期刊：
MESENCHYMAL STEM CELL ASSAYS AND APPLICATIONS
影响因子：
--
作者：
Fink, Trine;Zachar, Vladimir
通讯作者：
Zachar, Vladimir
影响因子：
5.4
作者：
El-Hage, Nazira;Dever, Seth M.;Hauser, Kurt F.
通讯作者：
Hauser, Kurt F.
影响因子：
25.7
作者：
Alter, MJ
通讯作者：
Alter, MJ
DOI：
10.1097/00126334-200104150-00011
发表时间：
2001-04-15
期刊：
JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
影响因子：
--
作者：
Daar, ES;Lynn, H;Winkler, CA
通讯作者：
Winkler, CA