Picornavirus VP2 protein suppresses innate immunity through selective autophagic degradation of IKBKE/IKKε.

ABSTRACT: Senecavirus A (SVA) belongs to the picornaviruses and has emerged as a promising candidate for oncolytic virotherapy in humans. Understanding the immune suppression mechanisms employed by SVA can help optimize its therapeutic efficacy as an oncolytic virus while simultaneously minimizing its immune suppressive effects on normal tissues. In this study, we identified a novel function of the SVA structural protein VP2 as a key viral immune suppressive factor during SVA infection. VP2 targets and degrades IKBKE/IKKε, a key component of the innate immune pathway, thereby suppressing host innate immune responses. It preferentially interacts with the selective autophagic receptor CALCOCO2/NDP52 (calcium binding and coiled-coil domain 2), which then recognizes the K33-linked ubiquitinated IKBKE an

SUBMITTER: Li K 

PROVIDER: S-EPMC12834145 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature