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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Systematic identification of type Ⅰ and type Ⅱ interferon-induced antiviral factors
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Systematic identification of type Ⅰ and type Ⅱ interferon-induced antiviral factors

机译：系统鉴定Ⅰ型和Ⅱ型干扰素诱导的抗病毒因子

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摘要

Type Ⅰ and type Ⅱ interferons (IFNs) are cytokines that establish the cellular antiviral state through the induction of IFN-stimulated genes (ISGs). We sought to understand the basis of the antiviral activity induced by type Ⅰ and Ⅱ IFNs in relation to the functions of their ISGs. Based on gene expression studies, we systematically identified antiviral ISGs by performing blinded, functional screens on 288 type Ⅰ and type Ⅱ ISGs. We assessed and validated the antiviral activity of these ISGs against an RNA virus, vesicular stomatitis virus (VSV), and a DNA virus, murine gammaherpes virus (MHV-68). Overall, we identified 34 ISGs that elicited an antiviral effect on the replication of either one or both viruses. Fourteen ISGs have uncharacterized. antiviral functions. We further defined ISGs that affect critical life-cycle processes in expression of VSV protein and MHV-68 immediate-early genes. Two previously undescribed antiviral ISGs, TAP1 and BMP2, were further validated.TAP1-deficient fibroblasts were more susceptible to VSV infection but less so to MHV-68 infection. On the other hand, exogenous BMP2 inhibits MHV-68 lytic growth but did not affect VSV growth. These results delineate common and distinct sets of type Ⅰ and type Ⅱ IFN-induced genes as well as identify unique ISGs that have either broad or specific antiviral effects on these viruses.
机译：Ⅰ型和Ⅱ型干扰素（IFN）是通过诱导IFN刺激基因（ISG）而建立细胞抗病毒状态的细胞因子。我们试图了解Ⅰ型和Ⅱ型IFN诱导的抗病毒活性与其ISG功能有关的基础。在基因表达研究的基础上，我们通过对288种Ⅰ型和Ⅱ型ISG进行盲法，功能性筛选，系统地鉴定了抗病毒ISG。我们评估并验证了这些ISG对RNA病毒，水疱性口炎病毒（VSV）和DNA病毒，鼠γ疱疹病毒（MHV-68）的抗病毒活性。总体而言，我们确定了34种ISG，它们对一种或两种病毒的复制均产生抗病毒作用。 14个ISG的特征不明确。抗病毒功能。我们进一步定义了ISV，这些ISG在VSV蛋白和MHV-68立即早期基因的表达中影响关键的生命周期过程。进一步验证了两个先前未描述的抗病毒ISG，即TAP1和BMP2。缺乏TAP1的成纤维细胞更易受VSV感染，而对MHV-68感染则较不敏感。另一方面，外源BMP2抑制MHV-68裂解生长，但不影响VSV生长。这些结果描述了由Ⅰ型和Ⅱ型IFN诱导的基因的常见和不同集合，并鉴定了对这些病毒具有广泛或特异性抗病毒作用的独特ISG。

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