title: A whole genome screen for HIV restriction factors.
abstract: BACKGROUND
  Upon cellular entry retroviruses must avoid innate restriction factors produced by the host cell. For human immunodeficiency virus (HIV) human restriction factors, APOBEC3 (apolipoprotein-B-mRNA-editing-enzyme), p21 and tetherin are well characterised.
  
  
  RESULTS
  To identify intrinsic resistance factors to HIV-1 replication we screened 19,121 human genes and identified 114 factors with significant inhibition of infection. Those with a known function are involved in a broad spectrum of cellular processes including receptor signalling, vesicle trafficking, transcription, apoptosis, cross-nuclear membrane transport, meiosis, DNA damage repair, ubiquitination and RNA processing. We focused on the PAF1 complex which has been previously implicated in gene transcription, cell cycle control and mRNA surveillance. Knockdown of all members of the PAF1 family of proteins enhanced HIV-1 reverse transcription and integration of provirus. Over-expression of PAF1 in host cells renders them refractory to HIV-1. Simian Immunodeficiency Viruses and HIV-2 are also restricted in PAF1 expressing cells. PAF1 is expressed in primary monocytes, macrophages and T-lymphocytes and we demonstrate strong activity in MonoMac1, a monocyte cell line.
  
  
  CONCLUSIONS
  We propose that the PAF1c establishes an anti-viral state to prevent infection by incoming retroviruses. This previously unrecognised mechanism of restriction could have implications for invasion of cells by any pathogen.
authors.affiliation: Centre for Immunology and Infectious Disease, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Nidia M M
authors.initials: NM
authors.lastname: Oliveira
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Cheney
authors.forename: Corinna
authors.initials: C
authors.lastname: Pade
authors.forename: Hanna
authors.initials: H
authors.lastname: Dreja
authors.forename: Ann-Marie H
authors.initials: AM
authors.lastname: Bergin
authors.forename: Viola
authors.initials: V
authors.lastname: Borgdorff
authors.forename: David H
authors.initials: DH
authors.lastname: Beach
authors.forename: Cleo L
authors.initials: CL
authors.lastname: Bishop
authors.forename: Matthias T
authors.initials: MT
authors.lastname: Dittmar
authors.forename: Aine
authors.initials: A
authors.lastname: McKnight
mesh_terms: D002460:Cell Line; D015894:Genome, Human; D006678:HIV / Q000235:genetics / Q000502:physiology*; D015658:HIV Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors; D014779:Virus Replication
chemical_list: D009687:Nuclear Proteins; C501972:PAF1 protein, human; D011506:Proteins; D014157:Transcription Factors
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