BclAF1 restriction factor is neutralized by proteasomal degradation and microRNA repression during human cytomegalovirus infection.
Cell proteins can restrict the replication of viruses. Here, we identify the cellular BclAF1 protein as a human cytomegalovirus restriction factor and describe two independent mechanisms the virus uses to decrease its steady-state levels. Immediately following infection, the viral pp71 and UL35 proteins, which are delivered to cells within virions, direct the proteasomal degradation of BclAF1. Although BclAF1 reaccumulates through the middle stages of infection, it is subsequently down-regulated at late times by miR-UL112-1, a virus-encoded microRNA. In the absence of BclAF1 neutralization, viral gene expression and replication are inhibited. These data identify two temporally and mechanistically distinct functions used by human cytomegalovirus to down-regulate a cellular antiviral protein.
Institute for Molecular Virology and McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI 53706, USA.
Song Hee
SH
Lee
Robert F
RF
Kalejta
Julie
J
Kerry
Oliver John
OJ
Semmes
Christine M
CM
O'Connor
Zia
Z
Khan
Benjamin A
BA
Garcia
Thomas
T
Shenk
Eain
E
Murphy
D003587:Cytomegalovirus / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000378:metabolism*; D017781:Genes, Immediate-Early; D006801:Humans; D006868:Hydrolysis; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D012097:Repressor Proteins / Q000276:immunology*; D025521:Tumor Suppressor Proteins / Q000276:immunology*
C119386:BCLAF1 protein, human; D035683:MicroRNAs; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D046988:Proteasome Endopeptidase Complex