Circulating hepatitis B surface antigen particles carry hepatocellular microRNAs.

Hepatitis B virus (HBV) produces high quantities of subviral surface antigen particles (HBsAg) which circulate in the blood outnumbering virions of about 1\10(3-6) times. In individuals coinfected with the defective hepatitis Delta virus (HDV) the small HDV-RNA-genome and Delta antigen circulate as...

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Autores principales: Luisa Novellino, Riccardo L Rossi, Ferruccio Bonino, Daniela Cavallone, Sergio Abrignani, Massimiliano Pagani, Maurizia R Brunetto
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:14fa10377ddc472aab5f610fc0dd89f22021-11-18T07:24:09ZCirculating hepatitis B surface antigen particles carry hepatocellular microRNAs.1932-620310.1371/journal.pone.0031952https://doaj.org/article/14fa10377ddc472aab5f610fc0dd89f22012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22470417/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Hepatitis B virus (HBV) produces high quantities of subviral surface antigen particles (HBsAg) which circulate in the blood outnumbering virions of about 1\10(3-6) times. In individuals coinfected with the defective hepatitis Delta virus (HDV) the small HDV-RNA-genome and Delta antigen circulate as ribonucleoprotein complexes within HBsAg subviral particles. We addressed the question whether subviral HBsAg particles may carry in the same way cellular microRNAs (miRNAs) which are released into the bloodstream within different subcellular forms such as exosomes and microvescicles. Circulating HBsAg particles were isolated from sera of 11 HBsAg carriers by selective immunoprecipitation with monoclonal anti-HBs-IgG, total RNA was extracted and human miRNAs were screened by TaqMan real-time quantitative PCR Arrays. Thirty-nine human miRNAs were found to be significantly associated with the immunoprecipitated HBsAg, as determined by both comparative DDCT analysis and non-parametric tests (Mann-Whitney, p<0.05) with respect to controls. Moreover immunoprecipitated HBsAg particles contained Ago2 protein that could be revealed in ELISA only after 0.5% NP40. HBsAg associated miRNAs were liver-specific (most frequent = miR-27a, miR-30b, miR-122, miR-126 and miR-145) as well as immune regulatory (most frequent = miR-106b and miR-223). Computationally predicted target genes of HBsAg-associated miRNAs highlighted molecular pathways dealing with host-pathogen. The finding that HBsAg particles carry selective pools of hepatocellular miRNAs opens new avenues of research to disentangle the complex interactions between host and HBV and provides a non invasive tool to study the physiopathology of liver epigenetics.Luisa NovellinoRiccardo L RossiFerruccio BoninoDaniela CavalloneSergio AbrignaniMassimiliano PaganiMaurizia R BrunettoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e31952 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Luisa Novellino
Riccardo L Rossi
Ferruccio Bonino
Daniela Cavallone
Sergio Abrignani
Massimiliano Pagani
Maurizia R Brunetto
Circulating hepatitis B surface antigen particles carry hepatocellular microRNAs.
description Hepatitis B virus (HBV) produces high quantities of subviral surface antigen particles (HBsAg) which circulate in the blood outnumbering virions of about 1\10(3-6) times. In individuals coinfected with the defective hepatitis Delta virus (HDV) the small HDV-RNA-genome and Delta antigen circulate as ribonucleoprotein complexes within HBsAg subviral particles. We addressed the question whether subviral HBsAg particles may carry in the same way cellular microRNAs (miRNAs) which are released into the bloodstream within different subcellular forms such as exosomes and microvescicles. Circulating HBsAg particles were isolated from sera of 11 HBsAg carriers by selective immunoprecipitation with monoclonal anti-HBs-IgG, total RNA was extracted and human miRNAs were screened by TaqMan real-time quantitative PCR Arrays. Thirty-nine human miRNAs were found to be significantly associated with the immunoprecipitated HBsAg, as determined by both comparative DDCT analysis and non-parametric tests (Mann-Whitney, p<0.05) with respect to controls. Moreover immunoprecipitated HBsAg particles contained Ago2 protein that could be revealed in ELISA only after 0.5% NP40. HBsAg associated miRNAs were liver-specific (most frequent = miR-27a, miR-30b, miR-122, miR-126 and miR-145) as well as immune regulatory (most frequent = miR-106b and miR-223). Computationally predicted target genes of HBsAg-associated miRNAs highlighted molecular pathways dealing with host-pathogen. The finding that HBsAg particles carry selective pools of hepatocellular miRNAs opens new avenues of research to disentangle the complex interactions between host and HBV and provides a non invasive tool to study the physiopathology of liver epigenetics.
format article
author Luisa Novellino
Riccardo L Rossi
Ferruccio Bonino
Daniela Cavallone
Sergio Abrignani
Massimiliano Pagani
Maurizia R Brunetto
author_facet Luisa Novellino
Riccardo L Rossi
Ferruccio Bonino
Daniela Cavallone
Sergio Abrignani
Massimiliano Pagani
Maurizia R Brunetto
author_sort Luisa Novellino
title Circulating hepatitis B surface antigen particles carry hepatocellular microRNAs.
title_short Circulating hepatitis B surface antigen particles carry hepatocellular microRNAs.
title_full Circulating hepatitis B surface antigen particles carry hepatocellular microRNAs.
title_fullStr Circulating hepatitis B surface antigen particles carry hepatocellular microRNAs.
title_full_unstemmed Circulating hepatitis B surface antigen particles carry hepatocellular microRNAs.
title_sort circulating hepatitis b surface antigen particles carry hepatocellular micrornas.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/14fa10377ddc472aab5f610fc0dd89f2
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AT ferrucciobonino circulatinghepatitisbsurfaceantigenparticlescarryhepatocellularmicrornas
AT danielacavallone circulatinghepatitisbsurfaceantigenparticlescarryhepatocellularmicrornas
AT sergioabrignani circulatinghepatitisbsurfaceantigenparticlescarryhepatocellularmicrornas
AT massimilianopagani circulatinghepatitisbsurfaceantigenparticlescarryhepatocellularmicrornas
AT mauriziarbrunetto circulatinghepatitisbsurfaceantigenparticlescarryhepatocellularmicrornas
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