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Investigation of the role of nuclear factors associated with double-stranded RNA protein members in the pathogenesis of HTLV-2

It has recently been demonstrated that HTLV-1 and HTLV-2 utilise antisense transcription to express the viral proteins, HBZ and APH-2, respectively. Studies have shown that HBZ is a key player in the pathogenesis of HTLV-1 as its temporal expression appears to be critical for the development of ATL and HAM/TSP. To date very little is known about the role of APH-2 in HTLV-2 infection. Thus, to investigate its role in the pathogenesis of HTLV-2, we recently performed yeast two hybrid screens of several cDNA libraries using APH-2 as bait. We identified a member of the Nuclear Factors Associated with double-stranded RNA (NFAR) proteins as a potential interacting protein of APH-2. The NFARs have been shown to be involved in the regulation of gene expression and most notably; host anti-viral defence. Our research affords the opportunity to investigate the interaction of APH-2 and NFARs and determine how this interaction impacts on HTLV-2 lifecycle events. Our findings indicate that APH-2 and NFARs interact in vivo and in vitro. Immunofluorescence demonstrates that APH-2 and NFARs localise to the nucleus. We have also performed knockdown studies to determine the effect of NFAR proteins on HTLV-2 LTR promoter activity. Our results reveal that NFARs exert no effect on basal LTR activation, but inhibit Tax2B-mediated viral transcription. Additionally we report that in the presence of APH-2, NFARs enhance Tax2B-mediated LTR activation. Overall, this study will provide novel insights into the functional role of APH-2 and NFAR proteins in the pathogenesis of HTLV-2.

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Correspondence to Noreen Sheehy.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( https://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated.

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Murphy, J.L., Hall, W.W. & Sheehy, N. Investigation of the role of nuclear factors associated with double-stranded RNA protein members in the pathogenesis of HTLV-2. Retrovirology 11, P113 (2014). https://doi.org/10.1186/1742-4690-11-S1-P113

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Keywords

  • cDNA Library
  • Nuclear Factor
  • Viral Protein
  • Temporal Expression
  • Viral Transcription