Deamidation, a type of post-translational modification commonly considered a hallmark of protein“aging” and function decay, is increasingly recognized for its pivotal role in regulating biologicalprocesses and viral...Deamidation, a type of post-translational modification commonly considered a hallmark of protein“aging” and function decay, is increasingly recognized for its pivotal role in regulating biologicalprocesses and viral infection. Our previous study has demonstrated that the deamidation of replicationand transcription activator (RTA), a master regulator of ubiquitous and oncogenic Kaposi's sarcomaassociated herpesvirus (KSHV), mediated by phosphoribosylformylglycinamidine synthetase (PFAS),hinders its nuclear import and transcriptional activity. Here we report that the viral glutamine amidotransferase (vGAT) pseudo-enzyme is exploited to facilitate KSHV lytic infection by inhibiting RTAdeamidation. To be more specific, vGAT interacts with both RTA and cellular PFAS, and inhibits PFASmediated RTA deamidation, thus facilitating RTA nuclear localization and suppressing nuclear factorkappa B (NF-κB) signaling activation, as well as augmenting RTA-mediated transcriptional activationof viral open reading frames (ORFs). In addition, vGAT appears to regulate the deamidation process ofseveral viral ORFs of KSHV. Collectively, these findings unveil that a viral pseudo-enzyme is exploitedto enhance viral infection via deamidation regulation.展开更多
基金funded by the National Natural Science Foundation of China(32173021)the Natural Science Foundation of Hunan Province(2024JJ5184)+2 种基金the Hunan Provincial Science&Technology Major Project(2022sfq30,20231F18)the Key Projects of Hunan Provincial Education Department(23A0196)the Earmarked Fund for Hunan Agriculture Research System(HARS-07).
文摘Deamidation, a type of post-translational modification commonly considered a hallmark of protein“aging” and function decay, is increasingly recognized for its pivotal role in regulating biologicalprocesses and viral infection. Our previous study has demonstrated that the deamidation of replicationand transcription activator (RTA), a master regulator of ubiquitous and oncogenic Kaposi's sarcomaassociated herpesvirus (KSHV), mediated by phosphoribosylformylglycinamidine synthetase (PFAS),hinders its nuclear import and transcriptional activity. Here we report that the viral glutamine amidotransferase (vGAT) pseudo-enzyme is exploited to facilitate KSHV lytic infection by inhibiting RTAdeamidation. To be more specific, vGAT interacts with both RTA and cellular PFAS, and inhibits PFASmediated RTA deamidation, thus facilitating RTA nuclear localization and suppressing nuclear factorkappa B (NF-κB) signaling activation, as well as augmenting RTA-mediated transcriptional activationof viral open reading frames (ORFs). In addition, vGAT appears to regulate the deamidation process ofseveral viral ORFs of KSHV. Collectively, these findings unveil that a viral pseudo-enzyme is exploitedto enhance viral infection via deamidation regulation.
