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

Song Hee Lee, Robert F. Kalejta, Julie Kerry, Oliver John Semmes, Christine M. O'Connor, Zia Khan, Benjamin A. Garcia, Thomas Shenk, Eain Murphy

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

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 twotemporally andmechanistically distinct functions used byhuman cytomegalovirus to down-regulate a cellular antiviral protein.

Original languageEnglish (US)
Pages (from-to)9575-9580
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number24
DOIs
StatePublished - Jun 12 2012

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Innate immunity
  • Intrinsic immunity
  • Proteasome
  • UL82
  • miRNA

Fingerprint Dive into the research topics of 'BclAF1 restriction factor is neutralized by proteasomal degradation and microRNA repression during human cytomegalovirus infection'. Together they form a unique fingerprint.

Cite this