MITA/STING and Its Alternative Splicing Isoform MRP Restrict Hepatitis B Virus Replication
An efficient clearance of hepatitis B virus (HBV) requires the coordinated work of both the innate and adaptive immune responses. MITA/STING, an adapter protein of the innate immune signaling pathways, plays a key role in regulating innate and adaptive immune responses to DNA virus infection. Previo...
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| creator | Liu, Shuhui Zhao, Kaitao Su, Xi Lu, Lu Zhao, He Zhang, Xianwen Wang, Yun Wu, Chunchen Chen, Jizheng Zhou, Yuan Hu, Xue Wang, Yanyi Lu, Mengji Chen, Xinwen Pei, Rongjuan |
| description | An efficient clearance of hepatitis B virus (HBV) requires the coordinated work of both the innate and adaptive immune responses. MITA/STING, an adapter protein of the innate immune signaling pathways, plays a key role in regulating innate and adaptive immune responses to DNA virus infection. Previously, we identified an alternatively spliced isoform of MITA/STING, called MITA-related protein (MRP), and found that MRP could specifically block MITA-mediated interferon (IFN) induction while retaining the ability to activate NF-κB. Here, we asked whether MITA/STING and MRP were able to control the HBV replication. Both MITA/STING and MRP significantly inhibited HBV replication in vitro. MITA overexpression stimulated IRF3-IFN pathway; while MRP overexpression activated NF-κB pathway, suggesting these two isoforms may inhibit HBV replication through different ways. Using a hydrodynamic injection (HI) mouse model, we found that HBV replication was reduced following MITA/STING and MRP expression vectors in mice and was enhanced by the knockout of MITA/STING (MITA/STING-/-). The HBV specific humoral and CD8+ T cell responses were impaired in MITA/STING deficient mice, suggesting the participation of MITA/STING in the initiation of host adaptive immune responses. In summary, our data suggest that MITA/STING and MRP contribute to HBV control via modulation of the innate and adaptive responses. |
| doi_str_mv | 10.1371/journal.pone.0169701 |
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MITA/STING, an adapter protein of the innate immune signaling pathways, plays a key role in regulating innate and adaptive immune responses to DNA virus infection. Previously, we identified an alternatively spliced isoform of MITA/STING, called MITA-related protein (MRP), and found that MRP could specifically block MITA-mediated interferon (IFN) induction while retaining the ability to activate NF-κB. Here, we asked whether MITA/STING and MRP were able to control the HBV replication. Both MITA/STING and MRP significantly inhibited HBV replication in vitro. MITA overexpression stimulated IRF3-IFN pathway; while MRP overexpression activated NF-κB pathway, suggesting these two isoforms may inhibit HBV replication through different ways. Using a hydrodynamic injection (HI) mouse model, we found that HBV replication was reduced following MITA/STING and MRP expression vectors in mice and was enhanced by the knockout of MITA/STING (MITA/STING-/-). The HBV specific humoral and CD8+ T cell responses were impaired in MITA/STING deficient mice, suggesting the participation of MITA/STING in the initiation of host adaptive immune responses. In summary, our data suggest that MITA/STING and MRP contribute to HBV control via modulation of the innate and adaptive responses.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0169701</identifier><identifier>PMID: 28056087</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adapter proteins ; Adapters ; Adaptive control ; Adaptive immunity ; Adenoviruses ; Alternative splicing ; Alternative Splicing - genetics ; Alternative Splicing - physiology ; Animals ; Antigens ; Biology and life sciences ; Blotting, Northern ; Blotting, Western ; CD8 antigen ; Deoxyribonucleic acid ; DNA ; Enzyme-Linked Immunosorbent Assay ; Expression vectors ; Genetic aspects ; Genetically modified mice ; Hepatitis ; Hepatitis B ; Hepatitis B virus ; Hepatitis B virus - genetics ; Hepatitis B virus - physiology ; Humans ; Immune clearance ; Immune response ; Immunohistochemistry ; Immunoprecipitation ; Infections ; Interferon ; Interferon regulatory factor 3 ; Isoforms ; Laboratories ; Liver - metabolism ; Liver cancer ; Lymphocytes ; Lymphocytes T ; Material requirements planning ; Medicine and Health Sciences ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Mice ; Mice, Knockout ; NF-κB protein ; Protein Isoforms - genetics ; Protein Isoforms - metabolism ; Real-Time Polymerase Chain Reaction ; Replication ; Research and Analysis Methods ; RNA Interference ; Rodents ; Signal Transduction - genetics ; Signal Transduction - physiology ; Signaling ; Stability ; Viral infections ; Virology ; Virus replication ; Virus Replication - genetics ; Virus Replication - physiology ; Viruses</subject><ispartof>PloS one, 2017-01, Vol.12 (1), p.e0169701-e0169701</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Liu et al 2017 Liu et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c725t-9d0174f53a8696cbcb9dd69a3da96ba0d413619e076056678bd47f27c750a5db3</citedby><cites>FETCH-LOGICAL-c725t-9d0174f53a8696cbcb9dd69a3da96ba0d413619e076056678bd47f27c750a5db3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215812/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215812/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2101,2927,23865,27923,27924,53790,53792,79471,79472</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28056087$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Guo, Haitao</contributor><creatorcontrib>Liu, Shuhui</creatorcontrib><creatorcontrib>Zhao, Kaitao</creatorcontrib><creatorcontrib>Su, Xi</creatorcontrib><creatorcontrib>Lu, Lu</creatorcontrib><creatorcontrib>Zhao, He</creatorcontrib><creatorcontrib>Zhang, Xianwen</creatorcontrib><creatorcontrib>Wang, Yun</creatorcontrib><creatorcontrib>Wu, Chunchen</creatorcontrib><creatorcontrib>Chen, Jizheng</creatorcontrib><creatorcontrib>Zhou, Yuan</creatorcontrib><creatorcontrib>Hu, Xue</creatorcontrib><creatorcontrib>Wang, Yanyi</creatorcontrib><creatorcontrib>Lu, Mengji</creatorcontrib><creatorcontrib>Chen, Xinwen</creatorcontrib><creatorcontrib>Pei, Rongjuan</creatorcontrib><title>MITA/STING and Its Alternative Splicing Isoform MRP Restrict Hepatitis B Virus Replication</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>An efficient clearance of hepatitis B virus (HBV) requires the coordinated work of both the innate and adaptive immune responses. MITA/STING, an adapter protein of the innate immune signaling pathways, plays a key role in regulating innate and adaptive immune responses to DNA virus infection. Previously, we identified an alternatively spliced isoform of MITA/STING, called MITA-related protein (MRP), and found that MRP could specifically block MITA-mediated interferon (IFN) induction while retaining the ability to activate NF-κB. Here, we asked whether MITA/STING and MRP were able to control the HBV replication. Both MITA/STING and MRP significantly inhibited HBV replication in vitro. MITA overexpression stimulated IRF3-IFN pathway; while MRP overexpression activated NF-κB pathway, suggesting these two isoforms may inhibit HBV replication through different ways. Using a hydrodynamic injection (HI) mouse model, we found that HBV replication was reduced following MITA/STING and MRP expression vectors in mice and was enhanced by the knockout of MITA/STING (MITA/STING-/-). The HBV specific humoral and CD8+ T cell responses were impaired in MITA/STING deficient mice, suggesting the participation of MITA/STING in the initiation of host adaptive immune responses. In summary, our data suggest that MITA/STING and MRP contribute to HBV control via modulation of the innate and adaptive responses.</description><subject>Adapter proteins</subject><subject>Adapters</subject><subject>Adaptive control</subject><subject>Adaptive immunity</subject><subject>Adenoviruses</subject><subject>Alternative splicing</subject><subject>Alternative Splicing - genetics</subject><subject>Alternative Splicing - physiology</subject><subject>Animals</subject><subject>Antigens</subject><subject>Biology and life sciences</subject><subject>Blotting, Northern</subject><subject>Blotting, Western</subject><subject>CD8 antigen</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Expression vectors</subject><subject>Genetic aspects</subject><subject>Genetically modified mice</subject><subject>Hepatitis</subject><subject>Hepatitis B</subject><subject>Hepatitis B virus</subject><subject>Hepatitis B virus - genetics</subject><subject>Hepatitis B virus - physiology</subject><subject>Humans</subject><subject>Immune clearance</subject><subject>Immune response</subject><subject>Immunohistochemistry</subject><subject>Immunoprecipitation</subject><subject>Infections</subject><subject>Interferon</subject><subject>Interferon regulatory factor 3</subject><subject>Isoforms</subject><subject>Laboratories</subject><subject>Liver - metabolism</subject><subject>Liver cancer</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Material requirements planning</subject><subject>Medicine and Health Sciences</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>NF-κB protein</subject><subject>Protein Isoforms - genetics</subject><subject>Protein Isoforms - metabolism</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Replication</subject><subject>Research and Analysis Methods</subject><subject>RNA Interference</subject><subject>Rodents</subject><subject>Signal Transduction - genetics</subject><subject>Signal Transduction - physiology</subject><subject>Signaling</subject><subject>Stability</subject><subject>Viral infections</subject><subject>Virology</subject><subject>Virus replication</subject><subject>Virus Replication - genetics</subject><subject>Virus Replication - physiology</subject><subject>Viruses</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11v0zAUhiMEYh_wDxBEQkJw0c4fsR3fTCoTbJE2htqyC24sx3FaV2lcbGca_x53zaYG7WLyha3j5319fOyTJO8gGEPM4MnKdq6VzXhjWz0GkHIG4IvkEHKMRhQB_HJvfZAceb8CgOCc0tfJAcoBoSBnh8nvq2I-OZnNix_nqWyrtAg-nTRBR-tgbnU62zRGmXaRFt7W1q3Tq-nPdKp9cEaF9EJvIhaMT7-mN8Z1Pm5tBTFo2zfJq1o2Xr_t5-Pk1_dv87OL0eX1eXE2uRwphkgY8QpAltUEy5xyqkpV8qqiXOJKclpKUGUQU8g1YDQmTVleVhmrEVOMAEmqEh8nH3a-m8Z60ZfFC5gTwhjhOI9EsSMqK1di48xaur_CSiPuA9YthHTBqEaLmkGAgVKcEZTlsOSQ1qVCqtRAK1Rn0eu0P60r17pSug1ONgPT4U5rlmJhbwVBkOQQRYPPvYGzf7pYSbE2Xummka223X3ePMsZRvQ5KCWcYkIi-vE_9OlC9NRCxruatrYxRbU1FZOMURqNKIzU-AkqjkqvjYrfrTYxPhB8GQgiE_RdWMjOe1HMps9nr2-G7Kc9dqllE5beNt32d_khmO1A5az3TteP7wGB2HbLQzXEtltE3y1R9n7_LR9FD-2B_wG65g0E</recordid><startdate>20170105</startdate><enddate>20170105</enddate><creator>Liu, Shuhui</creator><creator>Zhao, Kaitao</creator><creator>Su, Xi</creator><creator>Lu, Lu</creator><creator>Zhao, He</creator><creator>Zhang, Xianwen</creator><creator>Wang, Yun</creator><creator>Wu, Chunchen</creator><creator>Chen, Jizheng</creator><creator>Zhou, Yuan</creator><creator>Hu, Xue</creator><creator>Wang, Yanyi</creator><creator>Lu, Mengji</creator><creator>Chen, Xinwen</creator><creator>Pei, Rongjuan</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>20170105</creationdate><title>MITA/STING and Its Alternative Splicing Isoform MRP Restrict Hepatitis B Virus Replication</title><author>Liu, Shuhui ; Zhao, Kaitao ; Su, Xi ; Lu, Lu ; Zhao, He ; Zhang, Xianwen ; Wang, Yun ; Wu, Chunchen ; Chen, Jizheng ; Zhou, Yuan ; Hu, Xue ; Wang, Yanyi ; Lu, Mengji ; Chen, Xinwen ; Pei, Rongjuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c725t-9d0174f53a8696cbcb9dd69a3da96ba0d413619e076056678bd47f27c750a5db3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adapter proteins</topic><topic>Adapters</topic><topic>Adaptive control</topic><topic>Adaptive immunity</topic><topic>Adenoviruses</topic><topic>Alternative splicing</topic><topic>Alternative Splicing - genetics</topic><topic>Alternative Splicing - physiology</topic><topic>Animals</topic><topic>Antigens</topic><topic>Biology and life sciences</topic><topic>Blotting, Northern</topic><topic>Blotting, Western</topic><topic>CD8 antigen</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Expression vectors</topic><topic>Genetic aspects</topic><topic>Genetically modified mice</topic><topic>Hepatitis</topic><topic>Hepatitis B</topic><topic>Hepatitis B virus</topic><topic>Hepatitis B virus - genetics</topic><topic>Hepatitis B virus - physiology</topic><topic>Humans</topic><topic>Immune clearance</topic><topic>Immune response</topic><topic>Immunohistochemistry</topic><topic>Immunoprecipitation</topic><topic>Infections</topic><topic>Interferon</topic><topic>Interferon regulatory factor 3</topic><topic>Isoforms</topic><topic>Laboratories</topic><topic>Liver - metabolism</topic><topic>Liver cancer</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Material requirements planning</topic><topic>Medicine and Health Sciences</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>NF-κB protein</topic><topic>Protein Isoforms - genetics</topic><topic>Protein Isoforms - metabolism</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Replication</topic><topic>Research and Analysis Methods</topic><topic>RNA Interference</topic><topic>Rodents</topic><topic>Signal Transduction - genetics</topic><topic>Signal Transduction - physiology</topic><topic>Signaling</topic><topic>Stability</topic><topic>Viral infections</topic><topic>Virology</topic><topic>Virus replication</topic><topic>Virus Replication - genetics</topic><topic>Virus Replication - physiology</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Shuhui</creatorcontrib><creatorcontrib>Zhao, Kaitao</creatorcontrib><creatorcontrib>Su, Xi</creatorcontrib><creatorcontrib>Lu, Lu</creatorcontrib><creatorcontrib>Zhao, He</creatorcontrib><creatorcontrib>Zhang, Xianwen</creatorcontrib><creatorcontrib>Wang, Yun</creatorcontrib><creatorcontrib>Wu, Chunchen</creatorcontrib><creatorcontrib>Chen, Jizheng</creatorcontrib><creatorcontrib>Zhou, Yuan</creatorcontrib><creatorcontrib>Hu, Xue</creatorcontrib><creatorcontrib>Wang, Yanyi</creatorcontrib><creatorcontrib>Lu, Mengji</creatorcontrib><creatorcontrib>Chen, Xinwen</creatorcontrib><creatorcontrib>Pei, Rongjuan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection (ProQuest)</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Shuhui</au><au>Zhao, Kaitao</au><au>Su, Xi</au><au>Lu, Lu</au><au>Zhao, He</au><au>Zhang, Xianwen</au><au>Wang, Yun</au><au>Wu, Chunchen</au><au>Chen, Jizheng</au><au>Zhou, Yuan</au><au>Hu, Xue</au><au>Wang, Yanyi</au><au>Lu, Mengji</au><au>Chen, Xinwen</au><au>Pei, Rongjuan</au><au>Guo, Haitao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MITA/STING and Its Alternative Splicing Isoform MRP Restrict Hepatitis B Virus Replication</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-01-05</date><risdate>2017</risdate><volume>12</volume><issue>1</issue><spage>e0169701</spage><epage>e0169701</epage><pages>e0169701-e0169701</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>An efficient clearance of hepatitis B virus (HBV) requires the coordinated work of both the innate and adaptive immune responses. MITA/STING, an adapter protein of the innate immune signaling pathways, plays a key role in regulating innate and adaptive immune responses to DNA virus infection. Previously, we identified an alternatively spliced isoform of MITA/STING, called MITA-related protein (MRP), and found that MRP could specifically block MITA-mediated interferon (IFN) induction while retaining the ability to activate NF-κB. Here, we asked whether MITA/STING and MRP were able to control the HBV replication. Both MITA/STING and MRP significantly inhibited HBV replication in vitro. MITA overexpression stimulated IRF3-IFN pathway; while MRP overexpression activated NF-κB pathway, suggesting these two isoforms may inhibit HBV replication through different ways. Using a hydrodynamic injection (HI) mouse model, we found that HBV replication was reduced following MITA/STING and MRP expression vectors in mice and was enhanced by the knockout of MITA/STING (MITA/STING-/-). The HBV specific humoral and CD8+ T cell responses were impaired in MITA/STING deficient mice, suggesting the participation of MITA/STING in the initiation of host adaptive immune responses. In summary, our data suggest that MITA/STING and MRP contribute to HBV control via modulation of the innate and adaptive responses.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28056087</pmid><doi>10.1371/journal.pone.0169701</doi><tpages>e0169701</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2017-01, Vol.12 (1), p.e0169701-e0169701 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1855775938 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adapter proteins Adapters Adaptive control Adaptive immunity Adenoviruses Alternative splicing Alternative Splicing - genetics Alternative Splicing - physiology Animals Antigens Biology and life sciences Blotting, Northern Blotting, Western CD8 antigen Deoxyribonucleic acid DNA Enzyme-Linked Immunosorbent Assay Expression vectors Genetic aspects Genetically modified mice Hepatitis Hepatitis B Hepatitis B virus Hepatitis B virus - genetics Hepatitis B virus - physiology Humans Immune clearance Immune response Immunohistochemistry Immunoprecipitation Infections Interferon Interferon regulatory factor 3 Isoforms Laboratories Liver - metabolism Liver cancer Lymphocytes Lymphocytes T Material requirements planning Medicine and Health Sciences Membrane Proteins - genetics Membrane Proteins - metabolism Mice Mice, Knockout NF-κB protein Protein Isoforms - genetics Protein Isoforms - metabolism Real-Time Polymerase Chain Reaction Replication Research and Analysis Methods RNA Interference Rodents Signal Transduction - genetics Signal Transduction - physiology Signaling Stability Viral infections Virology Virus replication Virus Replication - genetics Virus Replication - physiology Viruses |
| title | MITA/STING and Its Alternative Splicing Isoform MRP Restrict Hepatitis B Virus Replication |
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