Huang Jiaying, Smirnov Sergey V, Lewis-Antes Anita, Balan Murugabaskar, Li Wei, Tang Sheila, Silke Gemma V, Pütz Mike M, Smith Geoffrey L, Kotenko Sergei V
Department of Biochemistry and Molecular Biology, University Hospital Cancer Center, New Jersey Medical School, Newark, NJ 07103, USA.
Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9822-7. doi: 10.1073/pnas.0610352104. Epub 2007 May 21.
Type I (IFN-alpha/beta) and type III (IFN-lambdas) IFNs are important components of the host antiviral response. Although type III IFNs possess intrinsic antiviral activity similar to that of type I IFNs, they signal through a specific unique receptor complex, and their functional importance for antiviral resistance is largely uncharacterized. Here, we report the first virus defense mechanism that directly targets type III IFNs. Y136 from Yaba-like disease virus, a yatapoxvirus, is a secreted glycoprotein related to protein B18 from Vaccinia virus, a known type I IFN-binding protein and a member of the Ig superfamily. Surprisingly, whereas B18 inhibits only type I IFNs, Y136 inhibits both type I and type III IFNs. Y136 inhibits IFN-induced signaling and suppresses IFN-mediated biological activities including up-regulation of MHC class I antigen expression and induction of the antiviral state. These data demonstrate that poxviruses have developed unique strategies to counteract IFN-mediated antiviral protection and highlight the importance of type III IFNs in antiviral defense. These results suggest that type III IFNs may be an effective treatment for some poxviral infections.
I型干扰素（IFN-α/β）和III型干扰素（IFN-λs）是宿主抗病毒反应的重要组成部分。尽管III型干扰素具有与I型干扰素相似的内在抗病毒活性，但它们通过一种特定的独特受体复合物进行信号传导，并且它们在抗病毒抗性方面的功能重要性在很大程度上尚未得到充分描述。在此，我们报道了第一种直接靶向III型干扰素的病毒防御机制。来自雅巴样疾病病毒（一种痘病毒）的Y136是一种分泌型糖蛋白，与痘苗病毒的B18蛋白相关，B18蛋白是一种已知的I型干扰素结合蛋白，属于免疫球蛋白超家族成员。令人惊讶的是，虽然B18仅抑制I型干扰素，但Y136同时抑制I型和III型干扰素。Y136抑制干扰素诱导的信号传导，并抑制干扰素介导的生物学活性，包括MHC I类抗原表达的上调和抗病毒状态的诱导。这些数据表明痘病毒已经发展出独特的策略来对抗干扰素介导的抗病毒保护，并突出了III型干扰素在抗病毒防御中的重要性。这些结果表明III型干扰素可能是治疗某些痘病毒感染的有效方法。
