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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| creator | Novellino, Luisa Rossi, Riccardo L Bonino, Ferruccio Cavallone, Daniela Abrignani, Sergio Pagani, Massimiliano Brunetto, Maurizia R |
| 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 |
| doi_str_mv | 10.1371/journal.pone.0031952 |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0031952</identifier><identifier>PMID: 22470417</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Analysis ; Antibodies - immunology ; Antigens ; Argonaute 2 protein ; Argonaute Proteins - analysis ; Argonaute Proteins - genetics ; Biology ; Cell growth ; Cloning ; Enzyme-linked immunosorbent assay ; Epigenetic inheritance ; Epigenetics ; Exosomes ; Female ; Genomes ; Genotype ; Hepatitis ; Hepatitis B ; Hepatitis B surface antigen ; Hepatitis B Surface Antigens - blood ; Hepatitis B Surface Antigens - immunology ; Hepatitis B Surface Antigens - metabolism ; Hepatitis B virus - metabolism ; Hepatitis delta Antigens - metabolism ; Hepatitis Delta Virus - metabolism ; Hepatology ; Host-Pathogen Interactions ; Hostages ; Humans ; Immune system ; Immunoglobulin G ; Immunoprecipitation ; Laboratories ; Liver ; Liver - metabolism ; Liver cancer ; Liver diseases ; Male ; Medicine ; MicroRNA ; MicroRNAs ; MicroRNAs - metabolism ; Middle Aged ; miRNA ; Particulates ; Proteins ; Ribonucleic acid ; RNA ; RNA polymerase ; Stem cells ; Virions ; Viruses</subject><ispartof>PloS one, 2012-03, Vol.7 (3), p.e31952-e31952</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Novellino et al. 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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.</description><subject>Adult</subject><subject>Analysis</subject><subject>Antibodies - immunology</subject><subject>Antigens</subject><subject>Argonaute 2 protein</subject><subject>Argonaute Proteins - analysis</subject><subject>Argonaute Proteins - genetics</subject><subject>Biology</subject><subject>Cell growth</subject><subject>Cloning</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Epigenetic inheritance</subject><subject>Epigenetics</subject><subject>Exosomes</subject><subject>Female</subject><subject>Genomes</subject><subject>Genotype</subject><subject>Hepatitis</subject><subject>Hepatitis B</subject><subject>Hepatitis B surface antigen</subject><subject>Hepatitis B Surface Antigens - blood</subject><subject>Hepatitis B Surface Antigens - immunology</subject><subject>Hepatitis B Surface Antigens - metabolism</subject><subject>Hepatitis B virus - metabolism</subject><subject>Hepatitis delta Antigens - metabolism</subject><subject>Hepatitis Delta Virus - metabolism</subject><subject>Hepatology</subject><subject>Host-Pathogen Interactions</subject><subject>Hostages</subject><subject>Humans</subject><subject>Immune system</subject><subject>Immunoglobulin G</subject><subject>Immunoprecipitation</subject><subject>Laboratories</subject><subject>Liver</subject><subject>Liver - metabolism</subject><subject>Liver cancer</subject><subject>Liver diseases</subject><subject>Male</subject><subject>Medicine</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - metabolism</subject><subject>Middle Aged</subject><subject>miRNA</subject><subject>Particulates</subject><subject>Proteins</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA polymerase</subject><subject>Stem cells</subject><subject>Virions</subject><subject>Viruses</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkkuP0zAUhSMEYobCP0AQCQnEosWvxMkGqVQ8Ko0YNDy21q0fqas0LraDmH-PQzOjBs0CZRHL_s659r0ny55itMCU4zc71_sO2sXBdXqBEMV1Qe5l57imZF4SRO-frM-yRyHsECpoVZYPszNCGEcM8_Psy8p62bcQbdfkW31Ii2hD_i4PvTcgdQ5dtI3u8gP4aGWrQy7B--sj66Ru26T2-d5K764-L8Pj7IGBNugn43-Wff_w_tvq0_zi8uN6tbyYS17wOFcUGWSY5ohrWm1qghnFklXAmKGgpIRSaSULBJWuFNUFMwRjqtmmMJuSF3SWPT_6HloXxNiMIDBlqGaE4SoR6yOhHOzEwds9-GvhwIq_G843YnyTwMwARpRzpSTjBCBVKTEyEilV1YYkr7djtX6zT_fSXfTQTkynJ53disb9EpRiVhKeDF6NBt797HWIYm_D0D3otOuDqEuWplUXA_niH_Lux41UA-n-tjMulZWDp1gyzhGqijT3Wba4g0qf0mlgKTjGpv2J4PVEkJiof8cG-hDE-uvV_7OXP6bsyxN2q6GN2-DaPlrXhSnIjmCKUwhem9seYySG3N90Qwy5F2Puk-zZ6XxuRTdBp38AcoP92w</recordid><startdate>20120328</startdate><enddate>20120328</enddate><creator>Novellino, Luisa</creator><creator>Rossi, Riccardo L</creator><creator>Bonino, Ferruccio</creator><creator>Cavallone, Daniela</creator><creator>Abrignani, Sergio</creator><creator>Pagani, Massimiliano</creator><creator>Brunetto, Maurizia R</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20120328</creationdate><title>Circulating hepatitis B surface antigen particles carry hepatocellular microRNAs</title><author>Novellino, Luisa ; Rossi, Riccardo L ; Bonino, Ferruccio ; Cavallone, Daniela ; Abrignani, Sergio ; Pagani, Massimiliano ; Brunetto, Maurizia R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c757t-d30f0f4e707e38b921431c48a44f3adcca6dedc50a8e8d3e54f2113e4b5fb6753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Analysis</topic><topic>Antibodies - immunology</topic><topic>Antigens</topic><topic>Argonaute 2 protein</topic><topic>Argonaute Proteins - analysis</topic><topic>Argonaute Proteins - genetics</topic><topic>Biology</topic><topic>Cell growth</topic><topic>Cloning</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Epigenetic inheritance</topic><topic>Epigenetics</topic><topic>Exosomes</topic><topic>Female</topic><topic>Genomes</topic><topic>Genotype</topic><topic>Hepatitis</topic><topic>Hepatitis B</topic><topic>Hepatitis B surface antigen</topic><topic>Hepatitis B Surface Antigens - blood</topic><topic>Hepatitis B Surface Antigens - immunology</topic><topic>Hepatitis B Surface Antigens - metabolism</topic><topic>Hepatitis B virus - metabolism</topic><topic>Hepatitis delta Antigens - metabolism</topic><topic>Hepatitis Delta Virus - metabolism</topic><topic>Hepatology</topic><topic>Host-Pathogen Interactions</topic><topic>Hostages</topic><topic>Humans</topic><topic>Immune system</topic><topic>Immunoglobulin G</topic><topic>Immunoprecipitation</topic><topic>Laboratories</topic><topic>Liver</topic><topic>Liver - 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22470417</pmid><doi>10.1371/journal.pone.0031952</doi><tpages>e31952</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-03, Vol.7 (3), p.e31952-e31952 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1340942418 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adult Analysis Antibodies - immunology Antigens Argonaute 2 protein Argonaute Proteins - analysis Argonaute Proteins - genetics Biology Cell growth Cloning Enzyme-linked immunosorbent assay Epigenetic inheritance Epigenetics Exosomes Female Genomes Genotype Hepatitis Hepatitis B Hepatitis B surface antigen Hepatitis B Surface Antigens - blood Hepatitis B Surface Antigens - immunology Hepatitis B Surface Antigens - metabolism Hepatitis B virus - metabolism Hepatitis delta Antigens - metabolism Hepatitis Delta Virus - metabolism Hepatology Host-Pathogen Interactions Hostages Humans Immune system Immunoglobulin G Immunoprecipitation Laboratories Liver Liver - metabolism Liver cancer Liver diseases Male Medicine MicroRNA MicroRNAs MicroRNAs - metabolism Middle Aged miRNA Particulates Proteins Ribonucleic acid RNA RNA polymerase Stem cells Virions Viruses |
| title | Circulating hepatitis B surface antigen particles carry hepatocellular microRNAs |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T21%3A55%3A45IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Circulating%20hepatitis%20B%20surface%20antigen%20particles%20carry%20hepatocellular%20microRNAs&rft.jtitle=PloS%20one&rft.au=Novellino,%20Luisa&rft.date=2012-03-28&rft.volume=7&rft.issue=3&rft.spage=e31952&rft.epage=e31952&rft.pages=e31952-e31952&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0031952&rft_dat=%3Cgale_plos_%3EA477008520%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1340942418&rft_id=info:pmid/22470417&rft_galeid=A477008520&rft_doaj_id=oai_doaj_org_article_14fa10377ddc472aab5f610fc0dd89f2&rfr_iscdi=true |