Castillo Ramirez Jorge Andrés, Urcuqui-Inchima Silvio
Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA , Medellín, Colombia .
J Interferon Cytokine Res. 2015 Jun;35(6):421-30. doi: 10.1089/jir.2014.0129. Epub 2015 Jan 28.
The arthropod-borne diseases caused by dengue virus (DENV) are a major and emerging problem of public health worldwide. Infection with DENV causes a series of clinical manifestations ranging from mild flu syndrome to severe diseases that include hemorrhage and shock. It has been demonstrated that the innate immune response plays a key role in DENV pathogenesis. However, in recent years, it was shown that DENV evades the innate immune response by blocking type I interferon (IFN-I). It has been demonstrated that DENV can inhibit both the production and the signaling of IFN-I. The viral proteins, NS2A and NS3, inhibit IFN-I production by degrading cellular signaling molecules. In addition, the viral proteins, NS2A, NS4A, NS4B, and NS5, can inhibit IFN-I signaling by blocking the phosphorylation of the STAT1 and STAT2 molecules. Finally, NS5 mediates the degradation of STAT2 using the proteasome machinery. In this study, we briefly review the most recent insights regarding the IFN-I response to DENV infection and its implication for pathogenesis.
由登革病毒（DENV）引起的虫媒疾病是全球公共卫生领域一个重大且不断出现的问题。感染DENV会引发一系列临床表现，从轻微流感综合征到包括出血和休克在内的严重疾病。已有研究表明，先天免疫反应在DENV发病机制中起关键作用。然而，近年来研究发现，DENV通过阻断I型干扰素（IFN-I）来逃避先天免疫反应。研究表明，DENV既能抑制IFN-I的产生，也能抑制其信号传导。病毒蛋白NS2A和NS3通过降解细胞信号分子来抑制IFN-I的产生。此外，病毒蛋白NS2A、NS4A、NS4B和NS5可通过阻断信号转导和转录激活因子1（STAT1）和信号转导和转录激活因子2（STAT2）分子的磷酸化来抑制IFN-I信号传导。最后，NS5利用蛋白酶体机制介导STAT2的降解。在本研究中，我们简要回顾了关于IFN-I对DENV感染的反应及其对发病机制影响的最新见解。
