A retrovirus restriction factor TRIM5α is transcriptionally regulated by interferons

Abstract

TRIM5α is a member of tripartite motif protein family and recently identified as a restriction factor for retroviral infection in a species-specific manner. Human TRIM5α gene is located on chromosomal position 11p15 in a cluster with other TRIM genes including TRIM6, 21, 22, and 34. We show here that interferon (IFN) upregulates TRIM5α mRNA expression in HeLa and HepG2 cells by performing Northern blot analysis and quantitative real-time PCR. TRIM5α promoter activity was IFN inducible as confirmed by luciferase assay using a reporter plasmid that contained the 5′-flanking region of TRIM5α. Mutational analysis has revealed that IFNs activate TRIM5α promoter activity through a putative interferon-stimulated response element (ISRE). Intriguingly, another IFN-responsive protein signal transducer and activator of transcription factor 1 (STAT1) binds to the ISRE sequence as shown by electrophoretic mobility shift assay using HeLa cell extracts. We have raised a specific polyclonal antibody against TRIM5α and confirmed that TRIM5α protein expression is inducible by IFN-β in HeLa cells. These results lead us to define that the transcription and protein synthesis of TRIM5α could be modulated by IFN, suggesting that TRIM5α may play a role in an IFN-induced antiviral state against retrovirus infection.