Cantrell Stacy R, Bresnahan Wade A
Department of Microbiology, University of Minnesota, 420 Delaware St., S.E., 1060 Mayo Building, MMC196, Minneapolis, MN 55455, USA.
J Virol. 2005 Jun;79(12):7792-802. doi: 10.1128/JVI.79.12.7792-7802.2005.
The human cytomegalovirus UL82-encoded pp71 protein is required for efficient virus replication and immediate-early gene expression when cells are infected at a low multiplicity. Functions attributed to pp71 include the ability to enhance the infectivity of viral DNA, bind to and target hypophosphorylated Rb family member proteins for degradation, drive quiescent cells into the cell cycle, and bind to the cellular protein hDaxx. Using UL82 mutant viruses, we demonstrate that the LXCXD motif within pp71 is not necessary for efficient virus replication in fibroblasts, suggesting that pp71's ability to degrade hypophosphorylated Rb family members and induce quiescent cells into the cell cycle is not responsible for the growth defect associated with a UL82 deletion mutant. However, UL82 mutants that cannot bind to hDaxx are unable to induce immediate-early gene expression and are severely attenuated for viral replication. These results indicate that the interaction between the human cytomegalovirus UL82 gene product (pp71) and hDaxx regulates immediate-early gene expression and viral replication.
当细胞以低感染复数被感染时，人巨细胞病毒UL82编码的pp71蛋白是高效病毒复制和即刻早期基因表达所必需的。赋予pp71的功能包括增强病毒DNA的感染性、结合并靶向低磷酸化的Rb家族成员蛋白以进行降解、驱使静止细胞进入细胞周期以及结合细胞蛋白hDaxx。使用UL82突变病毒，我们证明pp71内的LXCXD基序对于成纤维细胞中的高效病毒复制不是必需的，这表明pp71降解低磷酸化Rb家族成员并诱导静止细胞进入细胞周期的能力与UL82缺失突变体相关的生长缺陷无关。然而，不能结合hDaxx的UL82突变体无法诱导即刻早期基因表达，并且病毒复制严重减弱。这些结果表明人巨细胞病毒UL82基因产物（pp71）与hDaxx之间的相互作用调节即刻早期基因表达和病毒复制。
