Abstract
BackgroundIn this study, we have examined the role of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) in viral gene expression in T lymphocytes transformed by HTLV-1.ResultsWe have previously observed that hnRNP A1 (A1) down-modulates the post transcriptional activity of Rex protein of HTLV-1. Here, we tested whether the ectopic expression of a dominant negative mutant (NLS-A1-HA) defective in shuttling activity or knockdown of the hnRNPA1 gene using RNA interference could inhibit Rex-mediated export of viral mRNAs in HTLV-1 producing C91PL T-cells. We show that the expression of NLS-A1-HA does not modify the export of Rex-dependent viral mRNAs. Conversely, inhibiting A1 expression in C91PL cells by RNA interference provoked an increase in the Rex-dependent export of unspliced and singly spliced mRNAs. Surprisingly, we also observed a significant increase in proviral transcription and an accumulation of unspliced mRNAs, suggesting that the splicing process was affected. Finally, A1 knockdown in C91PL cells increased viral production by these cells. Thus, hnRNP A1 is implicated in the modulation of the level of HTLV-1 gene expression in T cells transformed by this human retrovirus.ConclusionsThese observations provide an insight into a new cellular control of HTLV-1 replication and suggest that hnRNP A1 is likely part of the regulatory mechanisms of the life cycle of this human retrovirus in T cells.
Highlights
In this study, we have examined the role of heterogeneous nuclear ribonucleoprotein A1 in viral gene expression in T lymphocytes transformed by HTLV-1
These observations provide an insight into a new cellular control of HTLV-1 replication and suggest that hnRNP A1 is likely part of the regulatory mechanisms of the life cycle of this human retrovirus in T cells
Confocal microscopy of untransduced (a) or NLS-A1-HA transduced (b)-C91PL cells after dual immunofluorescence staining with anti-HA and anti-hnRNP A1 antibodies; the right panels show the overlay of the green and red staining; dependent, these results indicate that the ectopic expression of the NLS-A1-HA mutant in C91 PL cells does not interfere with the functionality of Rex
Summary
We have examined the role of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) in viral gene expression in T lymphocytes transformed by HTLV-1. The 40-kDa Tax protein trans-activates transcription of the provirus, through its interaction with cellular transcription factors and with Tax response elements present in the 5' long terminal repeat (LTR). The post-transcriptional activity of the 27-kDa Rex protein, an RNA-binding protein, is mediated by its interaction with the Rex response element (XRE) located on the U3/R region of the 3'LTR present on all viral transcripts [9]. We have recently reported that heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) interferes with the binding of Rex to the XRE, leading to a functional impairment of this viral protein [12]
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