title: High frequency of alternative splicing of human genes participating in the HIV-1 life cycle: a model using TSG101, betaTrCP, PPIA, INI1, NAF1, and PML.
abstract: Alternative splicing may generate splice forms with different biologic roles or missing protein domains implicated in the interaction with HIV-1. To address this issue, 6 human genes were investigated-tumor suppressor gene 101 (TSG101), beta-transducin repeats containing protein (betaTrCP), peptidyl-proly cis-trans isomerase, cyclophilin A (PPIA), integrase interactor 1 protein (INI1), Nef-associated factor 1 (NAF1), and promyelacytic leukemia (PML)-involved in the viral life cycle and HIV-1 pathogenesis. All 6 genes presented alternative splicing, and a combined bioinformatic and reverse transcription polymerase chain reaction (RT-PCR) analysis identified 27 new variants for a total of 53 splice forms (an average of 9 variants per gene). The predicted frequency of the various splice forms based on expressed sequence tags (EST) analysis corresponded to the semiquantitative findings on RT-PCR analysis for the cell culture systems and for native CD4 cells investigated. Interindividual variation in the frequencies of various splice forms in CD4 T cells from blood donors was observed for INI1. Cell type-specific variation of splice pattern was observed for NAF1. Eight splice forms lacked or modified motifs implicated in the interaction with HIV-1, underscoring the potential interest of assessing alternative splicing when investigating viral cell biology and pathogenesis.
authors.affiliation: Division of Infectious Diseases and Institute of Microbiology, University Hospital of Lausanne, Switzerland.
authors.forename: Manuel
authors.initials: M
authors.lastname: Favre
authors.forename: Christophe
authors.initials: C
authors.lastname: Butticaz
authors.forename: Brian
authors.initials: B
authors.lastname: Stevenson
authors.forename: C Victor
authors.initials: CV
authors.lastname: Jongeneel
authors.forename: Amalio
authors.initials: A
authors.lastname: Telenti
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D002868:Chromosomal Proteins, Non-Histone; D019295:Computational Biology; D021984:Cyclophilin A / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D056827:Endosomal Sorting Complexes Required for Transport; D019204:GTP-Binding Proteins / Q000235:genetics; D005787:Gene Frequency; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins; D044844:beta-Transducin Repeat-Containing Proteins; D000099177:Tsg101 Protein
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D021984:Cyclophilin A; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D019204:GTP-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D000071796:SMARCB1 Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D044844:beta-Transducin Repeat-Containing Proteins; D000099177:Tsg101 Protein; C471644:BTRC protein, human; C513266:SMARCB1 protein, human; C117046:TNIP1 protein, human; C070576:PML protein, human