BclAF1 restriction factor is neutralized by proteasomal degradation and microRNA repression during human cytomegalovirus infection

Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9575-80. doi: 10.1073/pnas.1207496109. Epub 2012 May 29.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cytomegalovirus / genetics
  • Cytomegalovirus Infections / metabolism*
  • Genes, Immediate-Early
  • Humans
  • Hydrolysis
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / metabolism
  • Proteasome Endopeptidase Complex / metabolism*
  • Repressor Proteins / immunology*
  • Tumor Suppressor Proteins / immunology*


  • BCLAF1 protein, human
  • MicroRNAs
  • Repressor Proteins
  • Tumor Suppressor Proteins
  • Proteasome Endopeptidase Complex