Induction of antiviral cytidine deaminases does not explain the inhibition of hepatitis B virus replication by Interferons
Induction of antiviral cytidine deaminases does not explain the inhibition of hepatitis B virus replication by Interferons
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DOI：
10.1128/jvi.02489-06
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发表时间：
2007-10-01
影响因子：
5.4
通讯作者：
Trono, Didier
中科院分区：
文献类型：
--
作者：
Jost, Stephanie;Turelli, Priscilla;Trono, Didier
干扰素（IFN）在控制B型肝炎病毒（HBV）中起主要作用，无论是作为在感染的急性期期间限制病毒传播的内源性细胞因子还是作为用于治疗其慢性期的药物。然而，干扰素抑制HBV复制的机制至今仍不清楚。在这里，我们表明，I型和II型干扰素治疗的人肝细胞诱导生产APOBEC3G（A3G），并在较小程度上，APOBEC3F（A3F）和APOBEC3B（A3B），但不是其他两个胞苷脱氨酶也赋予抗HBV活性，激活诱导胞苷脱氨酶（AID），和APOBEC1。最重要的是，我们发现，阻断A3B，A3F和A3G相结合的RNA干扰和病毒粒子感染因子（Vif）蛋白的人类免疫缺陷病毒不会废除干扰素对HBV的抑制作用。我们的结论是，这些胞苷脱氨酶是不是IFN在其对这种病原体的作用必不可少的效应。
Interferons (IFNs) play a major role in the control of hepatitis B virus (HBV), whether as endogenous cytokines limiting the spread of the virus during the acute phase of the infection or as drugs for the treatment of its chronic phase. However, the mechanism by which IFNs inhibit HBV replication has so far remained elusive. Here, we show that type I and II IFN treatment of human hepatocytes induces the production of APOBEC3G (A3G) and, to a lesser extent, that of APOBEC3F (A3F) and APOBEC3B (A3B) but not that of two other cytidine deaminases also endowed with anti-HBV activity, activation-induced cytidine deaminase (AID), and APOBEC1. Most importantly, we reveal that blocking A3B, A3F, and A3G by combining RNA interference and the virion infectivity factor (Vif) protein of human immunodeficiency virus does not abrogate the inhibitory effect of IFNs on HBV. We conclude that these cytidine deaminases are not essential effectors of IFN in its action against this pathogen.