Activation of Toll-like receptor 3 impairs the dengue virus serotype 2 replication through induction of IFN-β in cultured hepatoma cells.
Activation of Toll-like receptor 3 impairs the dengue virus serotype 2 replication through induction of IFN-β in cultured hepatoma cells.
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DOI：
10.1371/journal.pone.0023346
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Huang X
中科院分区：
文献类型：
--
作者：
Liang Z;Wu S;Li Y;He L;Wu M;Jiang L;Feng L;Zhang P;Huang X
toll样受体（TLRs）在抵抗病原体入侵的先天免疫中起着重要作用。虽然TLR信号已被证明可以保护细胞免受几种病毒的感染，但TLR在登革热病毒（DENV）复制中的作用仍不清楚。在本研究中，我们通过用不同的TLR配体挑战肝癌细胞HepG2来检测DENV血清2型（DENV2）的复制。激活TLR3具有抗病毒作用，而预处理其他TLR配体（包括TLR1/2、TLR2/6、TLR4、TLR5或TLR7/8）的效果不显著。TLR3配体poly（I∶C）在病毒感染前或同时处理，但在处理后无显著下调病毒复制。聚（I∶C）预处理降低了病毒mRNA的表达和病毒染色阳性细胞，并伴有I型干扰素（IFN-β）和III型干扰素（IL-28A/B）的诱导。有趣的是，单独中和IFN-β成功地恢复了poly（I∶C）抑制的DENV2复制。IKK抑制剂可显著逆转IFN诱导和抑制DENV2的效应，进一步表明IFN-β是poly（I∶C）介导的抗病毒作用的主导因子。本研究首次证实了激活TLR3可通过IFN-β阻断DENV2复制，为poly（I∶C）可能是一种有前景的DENV感染免疫调节剂提供了实验线索，并可应用于临床预防。
Toll-like receptors (TLRs) play an important role in innate immunity against invading pathogens. Although TLR signaling has been indicated to protect cells from infection of several viruses, the role of TLRs in Dengue virus (DENV) replication is still unclear. In the present study, we examined the replication of DENV serotype 2 (DENV2) by challenging hepatoma cells HepG2 with different TLR ligands. Activation of TLR3 showed an antiviral effect, while pretreatment of other TLR ligands (including TLR1/2, TLR2/6, TLR4, TLR5 or TLR7/8) did not show a significant effect. TLR3 ligand poly(I∶C) treatment prior to viral infection or simultaneously, but not post-treatment, significantly down-regulated virus replication. Pretreatment with poly(I∶C) reduced viral mRNA expression and viral staining positive cells, accompanying an induction of the type I interferon (IFN-β) and type III IFN (IL-28A/B). Intriguingly, neutralization of IFN-β alone successfully restored the poly(I∶C)-inhibited replication of DENV2. The poly(I∶C)-mediated effects, including IFN induction and DENV2 suppression, were significantly reversed by IKK inhibitor, further suggesting that IFN-β is the dominant factor involved in the poly(I∶C) mediated antiviral effect. Our study presented the first evidence to show that activation of TLR3 is effective in blocking DENV2 replication via IFN-β, providing an experimental clue that poly(I∶C) may be a promising immunomodulatory agent against DENV infection and might be applicable for clinical prevention.