title: Modulation of TRIM5alpha activity in human cells by alternatively spliced TRIM5 isoforms.
abstract: TRIM5α is a restriction factor that can block an early step in the retroviral life cycle by recognizing and causing the disassembly of incoming viral capsids, thereby preventing the completion of reverse transcription. Numerous other isoforms of human TRIM5 exist, and isoforms lacking a C-terminal SPRY domain can inhibit the activity of TRIM5α. Thus, TRIM5α activity in a given cell type could be dependent on the relative proportions of TRIM5 isoforms expressed, but little information concerning the relative expression of TRIM5 isoforms in human cells is available. In this study, we demonstrate that mRNAs coding for TRIM5α represent only 50% of total TRIM5 transcripts in human cell lines, CD4(+) T cells, and macrophages. Transcripts coding for, in order of abundance, TRIM5ι (TRIM5-iota), a previously uncharacterized isoform, TRIM5γ, TRIM5δ, and TRIM5κ are also present. Like TRIM5γ and TRIM5δ, TRIM5ι and TRIM5κ do not inhibit HIV-1 replication, but both have dominant-negative activity against TRIM5α. Specific knockdown of TRIM5ι increases TRIM5α activity in human U373-X4 cells, indicating that physiological levels of expression of truncated TRIM5 isoforms in human cells can reduce the activity of TRIM5α.
authors.affiliation: INSERM U941, Paris 75010, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Battivelli
authors.forename: Julie
authors.initials: J
authors.lastname: Migraine
authors.forename: Denise
authors.initials: D
authors.lastname: Lecossier
authors.forename: Saori
authors.initials: S
authors.lastname: Matsuoka
authors.forename: Danielle
authors.initials: D
authors.lastname: Perez-Bercoff
authors.forename: Sentob
authors.initials: S
authors.lastname: Saragosti
authors.forename: François
authors.initials: F
authors.lastname: Clavel
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Hance
mesh_terms: D017398:Alternative Splicing; D000090103:Antiviral Restriction Factors; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D055785:Gene Knockdown Techniques; D006801:Humans; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms / Q000737:chemistry / Q000502:physiology*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D020033:Protein Isoforms; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases