In Vivo Interaction of the Hepatitis Delta Virus Small Antigen with the ELAV-Like Protein HuR



Ana Casaca1, Margarida Fardilha2, Edgar da Cruz e Silva2, Celso Cunha*, 1
1 Unidade de Biologia Molecular, Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa. Rua da Junqueira 100, 1349-008 Lisboa, Portugal
2 Laboratório de Transdução de Sinais, Centro de Biologia Celular, Universidade de Aveiro, Aveiro, Portugal


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© Casaca et al.; Licensee Bentham Open.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Unidade de Biologia Molecular, Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa. Rua da Junqueira 100, 1349-008 Lisboa, Portugal; Tel: +351213652620; Fax: +351213632105; E-mail: ccunha@ihmt.unl.pt


Abstract

The small and large delta antigens (S-HDAg and L-HDAg, respectively) represent two forms of the only protein encoded by the hepatitis delta virus (HDV) RNA genome. Consequently, HDV relies, at a large extent, on the host cell machinery for replication and transcription. Until now, only a limited number of cellular proteins were identified as S-HDAg or L-HDAg partners being involved in the modulation of the virus life cycle. In an attempt to identify cellular S-HDAg-binding proteins we made use of a yeast two-hybrid approach to screen a human liver cDNA library. We were able to identify HuR, a ubiquitously expressed protein involved in RNA stabilization, as an S-HDAg partner both in vitro and in vivo. HuR was found to be overexpressed and colocalize with HDAg in human hepatoma cells. siRNA knockdown of HuR mRNA resulted in inhibition of S-HDAg and L-HDAg expression.

Keywords: Hepatitis delta virus, delta antigen, yeast two-hybrid, HuR..