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Antisense protein of HTLV-2 (APH-2) associates with PML nuclear bodies: molecular determinants and functional implications

Antisens Protein of HTLV-2 (APH-2) was described in 2009. APH-2 mRNA is expressed in vivo in most HTLV-2 carriers. In recent years, several laboratories have searched for similarities and/or differences between APH-2 and the antisens protein of HTLV-1, HBZ. Similarly to HBZ, APH-2 negatively regulates HTLV-2 transcription. However, it does not promote cell proliferation. In vivo, APH-2 localizes in discrete nuclear domains distinct from nucleoli. We therefore characterized APH-2 subcellular localization, in order to decipher the determinants of such localization and to correlate it or not with APH-2 functions. We first identify APH-2-containing nuclear domains as PML nuclear bodies (PML-NB). PML-NB are modulators of a number of cellular processes ranging from transcription regulation to cell proliferation and death. We show that both an in silico-identified nuclear localization signal and the carboxy-terminal LXXLL motif contribute to APH-2 targeting to PML-NB. Covalent modification of APH-2 by SUMO-1 and non-covalent interaction between APH-2 and SUMO-1-modified cellular partners have also been investigated as mechanisms of APH-2 targeting to PML-NB. Our results further demonstrate that APH-2 association with PML-NB is critical for its ability to inhibit viral transcription. This association also leads to a striking decrease in APH-2 stability, suggesting that APH-2 might be active but also targeted to degradation in PML-NB. Finally, we show that APH-2 localization in PML-NB leads to PML-NB clustering and correlates with a decrease in cell proliferation. Altogether, our study sheds new light on the links between the subcellular localization of APH-2 and its cellular functions.

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Correspondence to Chloé Journo.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Journo, C., Turpin, J., Douceron, E. et al. Antisense protein of HTLV-2 (APH-2) associates with PML nuclear bodies: molecular determinants and functional implications. Retrovirology 11 (Suppl 1), P100 (2014).

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