Bovine infected-cell protein 0 (BICP0) encoded by bovine herpes virus 1 (BHV-1) immediate early gene is necessary for efficient productive infection, in a large part, because it activates all 3 classes of BHV-1 genes....Bovine infected-cell protein 0 (BICP0) encoded by bovine herpes virus 1 (BHV-1) immediate early gene is necessary for efficient productive infection, in a large part, because it activates all 3 classes of BHV-1 genes. It also has the ability to efficiently transactivate promoters that are not derived from BHV-1. To investigate the mechanism by which BICP0 achieves these effects, we expressed and purified BICP0 and its different mutants in E. coli. In vitro assays showed that both full-length BICP0 and its isolated RING finger domain induce the accumulation of polyubiquitin chains. Mutations within the RING finger region that abolish the in vitro ubiquitination activity also cause severe reduc- tions in BICP0 activity in other assays. Based on these, we conclude that BICP0 has the potential to act as an E3 ubiq- uitin ligase during viral infection and its RING finger do- main is necessary for this function. These strongly support the hypothesis that BICP0 might influence virus infection through its ability to interact with the ubiquitin-proteasome pathway.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.30170038)the Rising Star Program from Shanghai Municipal Government and the Distinguished Young Scholars Program from National Natural Science Foundation of China(Grant No.30225013).
文摘Bovine infected-cell protein 0 (BICP0) encoded by bovine herpes virus 1 (BHV-1) immediate early gene is necessary for efficient productive infection, in a large part, because it activates all 3 classes of BHV-1 genes. It also has the ability to efficiently transactivate promoters that are not derived from BHV-1. To investigate the mechanism by which BICP0 achieves these effects, we expressed and purified BICP0 and its different mutants in E. coli. In vitro assays showed that both full-length BICP0 and its isolated RING finger domain induce the accumulation of polyubiquitin chains. Mutations within the RING finger region that abolish the in vitro ubiquitination activity also cause severe reduc- tions in BICP0 activity in other assays. Based on these, we conclude that BICP0 has the potential to act as an E3 ubiq- uitin ligase during viral infection and its RING finger do- main is necessary for this function. These strongly support the hypothesis that BICP0 might influence virus infection through its ability to interact with the ubiquitin-proteasome pathway.
