Interaction between the human cytomegalovirus UL82 gene product (pp71) and hDaxx regulates immediate-early gene expression and viral replication.
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.
Cantrell
Stacy R
SR
Department of Microbiology, University of Minnesota, 420 Delaware St., S.E., 1060 Mayo Building, MMC196, Minneapolis, MN 55455, USA.
Bresnahan
Wade A
WA
D048868:Adaptor Proteins, Signal Transducing; D000956:Antigens, Viral / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D056970:Co-Repressor Proteins; D003587:Cytomegalovirus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity / Q000502:physiology; D015967:Gene Expression Regulation, Viral; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D018832:Molecular Chaperones; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
D048868:Adaptor Proteins, Signal Transducing; D000956:Antigens, Viral; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D014764:Viral Proteins; C044582:immediate-early proteins, cytomegalovirus; C051298:cytomegalovirus phosphoprotein 71kDa