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The heterogeneous ribonuclear protein C interacts with the hepatitis delta virus small antigen

BACKGROUND: Hepatitis delta virus (HDV) is considered to be a satellite virus of the Hepatitis B virus. The genome consists of a 1679 nt ssRNA molecule in which a single ORF was identified. This ORF codes for a unique protein, the Delta antigen (HDAg). During transcription, two forms, small (S-HDAg;...

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Autores principales: Casaca, Ana, Fardilha, Margarida, da Cruz e Silva, Edgar, Cunha, Celso
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160407/
https://www.ncbi.nlm.nih.gov/pubmed/21774814
http://dx.doi.org/10.1186/1743-422X-8-358
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author Casaca, Ana
Fardilha, Margarida
da Cruz e Silva, Edgar
Cunha, Celso
author_facet Casaca, Ana
Fardilha, Margarida
da Cruz e Silva, Edgar
Cunha, Celso
author_sort Casaca, Ana
collection PubMed
description BACKGROUND: Hepatitis delta virus (HDV) is considered to be a satellite virus of the Hepatitis B virus. The genome consists of a 1679 nt ssRNA molecule in which a single ORF was identified. This ORF codes for a unique protein, the Delta antigen (HDAg). During transcription, two forms, small (S-HDAg; p24) and large (L-HDAg; p27) of this antigen are derived as a result of an editing mechanism catalyzed by cellular adenosine deaminase 1. Despite its simplicity, little is still known about the host factors that interact with the virus RNA and antigens being to modulate virus replication. METHODS: A yeast two-hybrid screening of a human liver cDNA library, using the hepatitis delta virus (HDV) small antigen (S-HDAg) as bait, was performed. Blot overlay and co-immunoprecipitation assays were used in an attempt to confirm the interaction of hnRNPC and S-HDAg. siRNA knockdown assays of hnRNPC were performed to assess the effect on HDV antigen expression. RESULTS: Thirty known proteins were identified as S-HDAg interactors in the yeast two-hybrid screening. One of the identified proteins, hnRNPC, was found to interact with S-HDAg in vitro and in vivo in human liver cells. The interaction of the two proteins is mediated by the C-terminal half of the S-HDAg which contains a RNA-binding domain (aa 98-195). HDV RNA, S-HDAg, and hnRNPC, were also found to co-localize in the nucleus of human liver cells. Knockdown of hnRNPC mRNA using siRNAs resulted in a marked decreased expression of HDV antigens. CONCLUSIONS: S-HDAg was found to interact with human liver proteins previously assigned to different functional categories. Among those involved in nucleic acid metabolism, hnRNPC was found to interact in vitro and in vivo in human liver cells. Similar to other RNA viruses, it seems plausible that hnRNPC may also be involved in HDV replication. However, further investigation is mandatory to clarify this question.
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spelling pubmed-31604072011-08-24 The heterogeneous ribonuclear protein C interacts with the hepatitis delta virus small antigen Casaca, Ana Fardilha, Margarida da Cruz e Silva, Edgar Cunha, Celso Virol J Research BACKGROUND: Hepatitis delta virus (HDV) is considered to be a satellite virus of the Hepatitis B virus. The genome consists of a 1679 nt ssRNA molecule in which a single ORF was identified. This ORF codes for a unique protein, the Delta antigen (HDAg). During transcription, two forms, small (S-HDAg; p24) and large (L-HDAg; p27) of this antigen are derived as a result of an editing mechanism catalyzed by cellular adenosine deaminase 1. Despite its simplicity, little is still known about the host factors that interact with the virus RNA and antigens being to modulate virus replication. METHODS: A yeast two-hybrid screening of a human liver cDNA library, using the hepatitis delta virus (HDV) small antigen (S-HDAg) as bait, was performed. Blot overlay and co-immunoprecipitation assays were used in an attempt to confirm the interaction of hnRNPC and S-HDAg. siRNA knockdown assays of hnRNPC were performed to assess the effect on HDV antigen expression. RESULTS: Thirty known proteins were identified as S-HDAg interactors in the yeast two-hybrid screening. One of the identified proteins, hnRNPC, was found to interact with S-HDAg in vitro and in vivo in human liver cells. The interaction of the two proteins is mediated by the C-terminal half of the S-HDAg which contains a RNA-binding domain (aa 98-195). HDV RNA, S-HDAg, and hnRNPC, were also found to co-localize in the nucleus of human liver cells. Knockdown of hnRNPC mRNA using siRNAs resulted in a marked decreased expression of HDV antigens. CONCLUSIONS: S-HDAg was found to interact with human liver proteins previously assigned to different functional categories. Among those involved in nucleic acid metabolism, hnRNPC was found to interact in vitro and in vivo in human liver cells. Similar to other RNA viruses, it seems plausible that hnRNPC may also be involved in HDV replication. However, further investigation is mandatory to clarify this question. BioMed Central 2011-07-20 /pmc/articles/PMC3160407/ /pubmed/21774814 http://dx.doi.org/10.1186/1743-422X-8-358 Text en Copyright ©2011 Casaca et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Casaca, Ana
Fardilha, Margarida
da Cruz e Silva, Edgar
Cunha, Celso
The heterogeneous ribonuclear protein C interacts with the hepatitis delta virus small antigen
title The heterogeneous ribonuclear protein C interacts with the hepatitis delta virus small antigen
title_full The heterogeneous ribonuclear protein C interacts with the hepatitis delta virus small antigen
title_fullStr The heterogeneous ribonuclear protein C interacts with the hepatitis delta virus small antigen
title_full_unstemmed The heterogeneous ribonuclear protein C interacts with the hepatitis delta virus small antigen
title_short The heterogeneous ribonuclear protein C interacts with the hepatitis delta virus small antigen
title_sort heterogeneous ribonuclear protein c interacts with the hepatitis delta virus small antigen
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160407/
https://www.ncbi.nlm.nih.gov/pubmed/21774814
http://dx.doi.org/10.1186/1743-422X-8-358
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