Coinfection of Hepatic Cell Lines with Human Immunodeficiency Virus and Hepatitis B Virus Leads to an Increase in Intracellular Hepatitis B Surface Antigen
Coinfection of Hepatic Cell Lines with Human Immunodeficiency Virus and Hepatitis B Virus Leads to an Increase in Intracellular Hepatitis B Surface Antigen
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DOI：
10.1128/jvi.02594-09
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发表时间：
2010-06-01
影响因子：
5.4
通讯作者：
Lewin, Sharon R.
中科院分区：
文献类型：
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作者：
Iser, David M.;Warner, Nadia;Lewin, Sharon R.
在hiv -乙型肝炎病毒（HBV）合并感染的情况下，肝脏相关死亡率增加。然而，HIV和HBV之间的相互作用并没有解释这一观察结果。我们假设HIV感染肝细胞直接影响HBV的生命周期。我们用HIV实验室毒株（NL4-3和AD8）以及表达增强型绿色荧光蛋白（EGFP）的水疱性口炎病毒（VSV）假型HIV感染表达HBV （Hep3B和AD38细胞）或不表达HBV （Huh7、HepG2和AD43细胞）的人肝细胞系。在肝细胞系中NL4-3或AD8感染HIV后，我们观察到HIV逆转录酶活性显著增加，具有传染性。尽管流式细胞术未检测到AD38细胞表面CD4、CCR5和CXCR4，但马拉韦洛克抑制AD8感染AD38细胞，AMD3100抑制NL4-3，表明HIV通过CCR5或CXCR4进入AD38肝细胞系。使用vsv假型HIV实现了AD38细胞的高水平感染（50%）。通过Southern blotting或核酸信号扩增检测，AD38细胞系与HIV共感染未改变HBV DNA的数量或种类。然而，当采用Western blotting、定量HBsAg和荧光显微镜检测时，合并感染HIV与细胞内HBsAg显著增加相关。我们得出结论，HIV感染HBV感染的肝细胞系显著增加细胞内HBsAg，但不增加HBV DNA合成，并且继发于HIV直接感染的肝内HBsAg增加可能导致HIV-HBV合并感染个体的肝脏疾病加速。
Liver-related mortality is increased in the setting of HIV-hepatitis B virus (HBV) coinfection. However, interactions between HIV and HBV to explain this observation have not been described. We hypothesized that HIV infection of hepatocytes directly affects the life cycle of HBV. We infected human hepatic cell lines expressing HBV (Hep3B and AD38 cells) or not expressing HBV (Huh7, HepG2, and AD43 cells) with laboratory strains of HIV (NL4-3 and AD8), as well as a vesicular stomatitis virus (VSV)-pseudotyped HIV expressing enhanced green fluorescent protein (EGFP). Following HIV infection with NL4-3 or AD8 in hepatic cell lines, we observed a significant increase in HIV reverse transcriptase activity which was infectious. Despite no detection of surface CD4, CCR5, and CXCR4 by flow cytometry, AD8 infection of AD38 cells was inhibited by maraviroc and NL4-3 was inhibited by AMD3100, demonstrating that HIV enters AD38 hepatic cell lines via CCR5 or CXCR4. High-level infection of AD38 cells (50%) was achieved using VSV-pseudotyped HIV. Co-infection of the AD38 cell line with HIV did not alter the HBV DNA amount or species as determined by Southern blotting or nucleic acid signal amplification. However, coinfection with HIV was associated with a significant increase in intracellular HBsAg when measured by Western blotting, quantitative HBsAg, and fluorescence microscopy. We conclude that HIV infection of HBV-infected hepatic cell lines significantly increased intracellular HBsAg but not HBV DNA synthesis and that increased intrahepatic HBsAg secondary to direct infection by HIV may contribute to accelerated liver disease in HIV-HBV-coinfected individuals.