TY - JOUR T1 - BclAF1 restriction factor is neutralized by proteasomal degradation and microRNA repression during human cytomegalovirus infection JF - Proceedings of the National Academy of Sciences Y1 - 2012 A1 - Lee, Song Hee A1 - Kalejta, Robert F. A1 - Kerry, Julie A1 - Semmes, Oliver John A1 - O’Connor, Christine M. A1 - Zia Khan A1 - Garcia, Benjamin A. A1 - Shenk, Thomas A1 - Murphy, Eain KW - innate immunity KW - intrinsic immunity KW - miRNA KW - Proteasome KW - UL82 AB - 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. VL - 109 SN - 0027-8424, 1091-6490 UR - http://www.pnas.org/content/109/24/9575 CP - 24 J1 - PNAS ER -