| 论文摘要： |
p53, which regulates cell-cycle arrest and apoptosis, is a crucial target for viruses to release cells from cell-cycle checkpoints or to protect cells from apoptosis for their own benefit. Viral evasion mechanisms of aquatic viruses remain mysterious. Here, we report the spring viremia of carp virus (SVCV) degrading and stabilizing p53 in the ubiquitin-proteasome pathway by the N and P proteins, respectively. Early in an SVCV infection, significant induction was observed in the S phase and p53 was decreased in the protein level. Further experiments demonstrated that p53 interacted with SVCV N protein and was degraded by suppressing the K63-linked ubiquitination. However, the increase of p53 was observed late in the infection and experiments suggested that p53 was bound to SVCV P protein and stabilized by enhancing the K63-linked ubiquitination. Finally, lysine residue 358 was the key site for p53 K63-linked ubiquitination by the N and P proteins. Thus, our findings suggest that fish p53 is modulated by SVCV N and P protein in two distinct mechanisms, which uncovers the strategy for the subversion of p53-mediated host innate immune responses by aquatic viruses. Author summary Upon viral infiltration, host cells employ p53 to defend against infection. Thus, viruses need to inhibit these antiviral surveillance mechanisms in the host to efficiently spread to new hosts. To date, the evasion mechanisms against fish p53 remain unclear. In this study, we reveal that SVCV modulates host p53 expression by two distinct mechanisms. Through a series of experiments, we show that SVCV N protein bound and degraded host p53 through suppressing the K63-linked ubiquitination; SVCV P protein interacted with and stabilized p53 while enhancing the K63-linked ubiquitination; lysine residue 358 was the key site for p53 ubiquitination by the N and P proteins. Our findings shed light on the special evasion mechanisms of fish virus and expand our knowledge of the virus-host interactions that are responsible for regulating p53 in lower vertebrates. |
