title: LAP2alpha and BAF collaborate to organize the Moloney murine leukemia virus preintegration complex.
abstract: Integration of viral DNA into the host genome is an essential step in retroviral replication. The viral DNA made by reverse transcription is a component of the preintegration complex (PIC) that also contains the viral integrase protein, the enzyme that integrates the viral DNA. Several other viral and cellular proteins are present in the PIC, but their functional roles are less well established. Barrier-to-autointegration factor (BAF) is a cellular protein component of the PIC that blocks autointegration of the viral DNA and stimulates intermolecular integration. In uninfected cells, BAF interacts with members of the LEM family of inner nuclear membrane and nucleoplasmic proteins. Here, we demonstrate that one of the LEM proteins, lamina-associated polypeptide 2alpha (LAP2alpha), is a component of the PIC. LAP2alpha stabilizes the association of BAF with the PIC to stimulate intermolecular integration and suppress autointegration. To further understand the role of LAP2alpha, we established LAP2alpha-knockdown cell lines. Depletion of LAP2alpha significantly inhibited viral replication. Our results demonstrate a critical contribution of LAP2alpha to the nucleoprotein organization of the PIC and to viral replication.
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0560, USA.
authors.forename: Youichi
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Hongfei
authors.initials: H
authors.lastname: Yang
authors.forename: Robert
authors.initials: R
authors.lastname: Craigie
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology; D004279:DNA, Viral / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011189:Potassium Chloride / Q000737:chemistry; D034741:RNA, Small Interfering / Q000378:metabolism; D048348:Reverse Transcription; D016662:Virus Integration / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication / Q000235:genetics / Q000502:physiology*
chemical_list: C501960:Banf1 protein, mouse; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C093413:lamina-associated polypeptide 2; D011189:Potassium Chloride