Affiliation:
1. INSERM U941, Paris 75010, France
2. Institut Universitaire d'Hématologie, Université Paris Diderot, Hôpital Saint-Louis, Paris 75010, France
3. Service des Maladies Infectieuses et Tropicales, Assistance Publique—Hôpitaux de Paris, Hôpital Bichat—Claude Bernard, Paris 75018, France
Abstract
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.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Cited by
34 articles.
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