Fatty acid biosynthesis is involved in the production of hepatitis B virus particles
Fatty acid biosynthesis is involved in the production of hepatitis B virus particles
复制标题
DOI：
10.1016/j.bbrc.2016.05.043
复制
发表时间：
2016-06-17
影响因子：
3.1
通讯作者：
Hijikata, Makoto
中科院分区：
文献类型：
--
作者：
Okamura, Hitomi;Nio, Yasunori;Hijikata, Makoto
乙型肝炎病毒（HBV）感染后在肝细胞中增殖，但在分子水平上对促进HBV生命周期的宿主因素知之甚少。最近有报道称脂肪酸生物合成（FABS）促进了丙型肝炎病毒的基因组复制，我们研究了脂肪酸生物合成（FABS）是否在HBV增殖中起作用。我们利用重组HBV产生的培养细胞检测了FABS通路中酶抑制剂对HBV生命周期的影响，发现细胞外HBV DNA水平（反映HBV颗粒的产生）通过抑制长链饱和脂肪酸合成的抑制剂治疗而降低，而细胞毒性很小。当脂肪酸合成酶（FAS）在FABS过程中的产物棕榈酸与抑制剂同时使用时，降低的HBV DNA水平被逆转。我们还观察到，通过FAS抑制剂治疗，细胞内HBV DNA的数量增加，这表明FABS与HBV颗粒产生有关，但与其基因组复制无关。这表明FABS可能是抗HBV药物的有效靶点，其作用模式不同于目前的HBV治疗。(C) 2016 Elsevier Inc.版权所有。
Hepatitis B virus (HBV) proliferates in hepatocytes after infection, but the host factors that contribute to the HBV lifecycle are poorly understood at the molecular level. We investigated whether fatty acid biosynthesis (FABS), which was recently reported to contribute to the genomic replication of hepatitis C virus, plays a role in HBV proliferation. We examined the effects of inhibitors of the enzymes in the FABS pathway on the HBV lifecycle by using recombinant HBV-producing cultured cells and found that the extracellular HBV DNA level, reflecting HBV particle production, was decreased by treatment with inhibitors suppressed the synthesis of long-chain saturated fatty acids with little cytotoxicity. The reduced HBV DNA level was reversed when palmitic acid, which is the product of fatty acid synthase (FAS) during FABS, was used simultaneously with the inhibitor. We also observed that the amount of intracellular HBV DNA in the cells was increased by FAS inhibitor treatment, suggesting that FABS is associated with HBV particle production but not its genome replication. This suggests that FABS might be a potent target for anti-HBV drug with a mode of action different from current HBV therapy. (C) 2016 Elsevier Inc. All rights reserved.