Intrahepatic induction of alpha/beta interferon eliminates viral RNA-containing capsids in hepatitis B virus transgenic mice
Intrahepatic induction of alpha/beta interferon eliminates viral RNA-containing capsids in hepatitis B virus transgenic mice
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DOI：
10.1128/jvi.74.9.4165-4173.2000
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发表时间：
2000-05-01
影响因子：
5.4
通讯作者：
Chisari, FV
中科院分区：
文献类型：
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作者：
Wieland, SF;Guidotti, LG;Chisari, FV
我们之前的研究表明，通过在肝脏中诱导α / β干扰素（ifn - α / β）的刺激，乙型肝炎病毒（HBV）的复制在HBV转基因小鼠的肝脏中被消除。本研究旨在确定ifn - α / β诱导剂多肌苷-多胞苷酸[poly(1-C)]对转基因小鼠HBV复制过程中受该细胞因子影响的步骤。我们发现，在poly（1-C）给药后9小时内，含有HBV前基因组RNA （pgRNA）的细胞质衣壳库减少了10倍，而HBV mRNA的丰度和细胞质HBV转录物的翻译状态没有变化。此外，我们发现，至少在处理后15小时，含HBV dna的衣壳库才会减少到相同的程度，并且我们发现病毒输出不会加速，血清中病毒粒子的半衰期不变。这些结果表明，ifn - α / β触发细胞内事件，抑制含有pgrna的衣壳的组装或加速其降解，并且病毒的成熟和分泌负责清除肝细胞细胞质中的HBV衣壳及其复制中间体。
We have previously shown that hepatitis B virus (HBV) replication is abolished in the liver of HBV transgenic mice by stimuli that induce alpha/beta interferon (IFN-alpha/beta) in the liver. The present study was done to identify the step(s) in HBV replication that is affected by this cytokine in transgenic mice treated with the IFN-alpha/beta inducer polyinosinic-polycytidylic acid [poly(1-C)], Here we show that the pool of cytoplasmic HBV pregenomic RNA (pgRNA)-containing capsids is reduced 10-Fold within 9 h after poly(1-C) administration, while there is no change in the abundance of HBV mRNA or in the translational status of cytoplasmic HBV transcripts. In addition, we show that the pool of HBV DNA-containing capsids is not reduced to the same degree until at least 15 h posttreatment, and we show that virus export is not accelerated and the half-life of virions in the serum is unchanged. These results indicate that IFN-alpha/beta triggers intracellular events that either inhibit the assembly of pgRNA-containing capsids or accelerate their degradation, and that maturation and secretion of virus is responsible for clearance of HBV capsids and their cargo of replicative intermediates from the cytoplasm of the hepatocyte.