Enterovirus D68 Protease 2A<sup>pro</sup>Targets TRAF3 To Subvert Host Innate Immune Responses
Jun Kang, Zheng Pang, Zhenwei Zhou, Xianhuang Li, Sihua Liu, Jinyan Cheng, Peiyuan Liu, Wenjie Tan, Zhiyun Wang, Tao Wang
Abstract
Human enterovirus 68 (EV-D68) has received considerable attention recently as a global reemergent pathogen because it causes severe respiratory tract infections and acute flaccid myelitis. The nonstructural protein 2A protease (2A pro ) of EV, which functions in cleavage of host proteins, comprises an essential part of the viral immune evasion process. However, the pathogenic mechanism of EV-D68 is not fully understood. Here, we show for the first time that EV-D68 inhibited antiviral type I interferon responses by cleaving tumor necrosis factor receptor-associated factor 3 (TRAF3). Furthermore, we identified the key cleavage site in TRAF3. Our study may suggest a new mechanism by which the 2A pro of EV facilitates subversion of host innate immune responses. These findings increase our understanding of EV-D68 infection and may help identify new antiviral targets against EV-D68.