Inhibition of type Ⅰ and type Ⅲ interferons by a secreted glycoprotein from Yaba-like disease virus

摘要

Type Ⅰ (IFN-α/β) and type Ⅲ (IFN-λs) 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.