Department of Virology, University of Freiburg, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany.
J Virol. 2010 Jun;84(11):5670-7. doi: 10.1128/JVI.00272-10. Epub 2010 Mar 24.
Virus-infected cells secrete a broad range of interferons (IFN) which confer resistance to yet uninfected cells by triggering the synthesis of antiviral factors. The relative contributions of the various IFN subtypes to innate immunity against virus infections remain elusive. IFN-alpha, IFN-beta, and other type I IFN molecules signal through a common, universally expressed cell surface receptor, whereas type III IFN (IFN-lambda) uses a distinct cell-type-specific receptor complex for signaling. Using mice lacking functional receptors for type I IFN, type III IFN, or both, we found that IFN-lambda plays an important role in the defense against several human pathogens that infect the respiratory tract, such as influenza A virus, influenza B virus, respiratory syncytial virus, human metapneumovirus, and severe acute respiratory syndrome (SARS) coronavirus. These viruses were more pathogenic and replicated to higher titers in the lungs of mice lacking both IFN receptors than in mice with single IFN receptor defects. In contrast, Lassa fever virus, which infects via the respiratory tract but primarily replicates in the liver, was not influenced by the IFN-lambda receptor defect. Careful analysis revealed that expression of functional IFN-lambda receptor complexes in the lung and intestinal tract is restricted to epithelial cells and a few other, undefined cell types. Interestingly, we found that SARS coronavirus was present in feces from infected mice lacking receptors for both type I and type III IFN but not in those from mice lacking single receptors, supporting the view that IFN-lambda contributes to the control of viral infections in epithelial cells of both respiratory and gastrointestinal tracts.
受病毒感染的细胞会分泌出广泛的干扰素 (IFN)，通过触发抗病毒因子的合成，使未感染的细胞产生抵抗力。不同的 IFN 亚型对先天免疫抵抗病毒感染的相对贡献仍然难以捉摸。IFN-α、IFN-β 和其他 I 型 IFN 分子通过共同的、普遍表达的细胞表面受体信号传递，而 III 型 IFN（IFN-λ）则使用独特的细胞类型特异性受体复合物进行信号传递。使用缺乏功能性 I 型 IFN、III 型 IFN 或两者受体的小鼠，我们发现 IFN-λ 在防御几种感染呼吸道的人类病原体方面发挥着重要作用，例如甲型流感病毒、乙型流感病毒、呼吸道合胞病毒、人类偏肺病毒和严重急性呼吸综合征 (SARS) 冠状病毒。这些病毒在缺乏两种 IFN 受体的小鼠肺部中的致病性更强，复制到更高的滴度，而在具有单一 IFN 受体缺陷的小鼠中则不是这样。相比之下，通过呼吸道感染但主要在肝脏中复制的拉沙热病毒不受 IFN-λ 受体缺陷的影响。仔细分析表明，功能性 IFN-λ 受体复合物在肺部和肠道中的表达仅限于上皮细胞和其他少数未定义的细胞类型。有趣的是，我们发现 SARS 冠状病毒存在于缺乏 I 型和 III 型 IFN 受体的感染小鼠的粪便中，但不存在于缺乏单一受体的小鼠的粪便中，这支持了 IFN-λ 有助于控制呼吸道和胃肠道上皮细胞中病毒感染的观点。
