Replication in cells of hematopoietic origin is necessary for Dengue virus dissemination
Dengue virus (DENV) is a mosquito-borne pathogen for which no vaccine or specific therapeutic is available. Although it is well established that dendritic cells and macrophages are primary sites of DENV replication, it remains unclear whether non-hematopoietic cellular compartments serve as virus re...
Gespeichert in:
| Veröffentlicht in: | PLoS pathogens 2012-01, Vol.8 (1), p.e1002465-e1002465 |
|---|---|
| Hauptverfasser: | , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e1002465 |
|---|---|
| container_issue | 1 |
| container_start_page | e1002465 |
| container_title | PLoS pathogens |
| container_volume | 8 |
| creator | Pham, Alissa M Langlois, Ryan A TenOever, Benjamin R |
| description | Dengue virus (DENV) is a mosquito-borne pathogen for which no vaccine or specific therapeutic is available. Although it is well established that dendritic cells and macrophages are primary sites of DENV replication, it remains unclear whether non-hematopoietic cellular compartments serve as virus reservoirs. Here, we exploited hematopoietic-specific microRNA-142 (miR-142) to control virus tropism by inserting tandem target sites into the virus to restrict replication exclusively in this cell population. In vivo use of this virus restricted infection of CD11b+, CD11c+, and CD45+ cells, resulting in a loss of virus spread, regardless of the route of administration. Furthermore, sequencing of the targeted virus population that persisted at low levels, demonstrated total excision of the inserted miR-142 target sites. The complete conversion of the virus population under these selective conditions suggests that these immune cells are the predominant sources of virus amplification. Taken together, this work highlights the importance of hematopoietic cells for DENV replication and showcases an invaluable tool for the study of virus pathogenesis. |
| doi_str_mv | 10.1371/journal.ppat.1002465 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1289100070</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A280004878</galeid><doaj_id>oai_doaj_org_article_91c8791db0024488ab8fa4f89ac5ede3</doaj_id><sourcerecordid>A280004878</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-594c8a5ffbc6260b6a79f03e5911578de1a74bc41a3337aa0a2181c79b3e91693</originalsourceid><addsrcrecordid>eNqVk99r1TAUx4sobk7_A9GCD-LDvSZN0iQvwpi_LgyFqeBbOE1Pu4zepkvaof-96W43dmUgkoeE5HO-OeebnCx7TsmaMknfXvgp9NCthwHGNSWk4KV4kB1SIdhKMskf3lkfZE9ivCCEU0bLx9lBURScak0Ps59nOHTOwuh8n7s-t9h1MfdNfo5bGP3gHY7O5j64Np26mPdoMUYIv_PGh_w99u2E-ZULU8xrFyNuXX8t9jR71EAX8dkyH2U_Pn74fvJ5dfr10-bk-HRlS12MK6G5VSCaprJlUZKqBKkbwlBoSoVUNVKQvLKcAmNMAhAoqKJW6oqhpqVmR9nLne7Q-WgWU6KhhdLJFCJJIjY7ovZwYYbgtil748GZ6w0fWgMhFdmh0dQqqWldzXZypaBSDfBGabACa2RJ691y21RtsbbYjwG6PdH9k96dm9ZfGVaIgpUqCbxeBIK_nDCOZuvibDr06KdotOAl01qX_yZpSQWRYi7w1V_k_TYsVAupUtc3PiVoZ01zXKjEcCXn_Nb3UGnU6WWt77FxaX8v4M1eQGJG_DW2MMVoNt_O_oP9ss_yHWuDjzFgc2syJWZugJsizdwAZmmAFPbi7gPdBt38ePYHQf4AxA</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1289100070</pqid></control><display><type>article</type><title>Replication in cells of hematopoietic origin is necessary for Dengue virus dissemination</title><source>Public Library of Science (PLoS) Journals Open Access</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>PubMed Central Open Access</source><creator>Pham, Alissa M ; Langlois, Ryan A ; TenOever, Benjamin R</creator><contributor>Kuhn, Richard J.</contributor><creatorcontrib>Pham, Alissa M ; Langlois, Ryan A ; TenOever, Benjamin R ; Kuhn, Richard J.</creatorcontrib><description>Dengue virus (DENV) is a mosquito-borne pathogen for which no vaccine or specific therapeutic is available. Although it is well established that dendritic cells and macrophages are primary sites of DENV replication, it remains unclear whether non-hematopoietic cellular compartments serve as virus reservoirs. Here, we exploited hematopoietic-specific microRNA-142 (miR-142) to control virus tropism by inserting tandem target sites into the virus to restrict replication exclusively in this cell population. In vivo use of this virus restricted infection of CD11b+, CD11c+, and CD45+ cells, resulting in a loss of virus spread, regardless of the route of administration. Furthermore, sequencing of the targeted virus population that persisted at low levels, demonstrated total excision of the inserted miR-142 target sites. The complete conversion of the virus population under these selective conditions suggests that these immune cells are the predominant sources of virus amplification. Taken together, this work highlights the importance of hematopoietic cells for DENV replication and showcases an invaluable tool for the study of virus pathogenesis.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1002465</identifier><identifier>PMID: 22241991</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Antigens, CD - genetics ; Antigens, CD - immunology ; Antigens, CD - metabolism ; Biology ; Bone marrow cells ; Cloning ; Dengue - genetics ; Dengue - immunology ; Dengue - metabolism ; Dengue fever ; Dengue virus ; Dengue Virus - physiology ; Dengue viruses ; Distribution ; Genetic aspects ; Genomes ; Health aspects ; HEK293 Cells ; Hematopoietic Stem Cells - immunology ; Hematopoietic Stem Cells - metabolism ; Hematopoietic Stem Cells - virology ; Heparan sulfate ; Humans ; Infections ; Lymphatic system ; Mice ; Mice, Knockout ; MicroRNAs - genetics ; MicroRNAs - immunology ; MicroRNAs - metabolism ; Mutation ; Pathogenesis ; Physiological aspects ; Population ; Proteins ; Virus Replication - physiology ; Viruses</subject><ispartof>PLoS pathogens, 2012-01, Vol.8 (1), p.e1002465-e1002465</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Pham et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Pham AM, Langlois RA, tenOever BR (2012) Replication in Cells of Hematopoietic Origin Is Necessary for Dengue Virus Dissemination. PLoS Pathog 8(1): e1002465. doi:10.1371/journal.ppat.1002465</rights><rights>Pham et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-594c8a5ffbc6260b6a79f03e5911578de1a74bc41a3337aa0a2181c79b3e91693</citedby><cites>FETCH-LOGICAL-c692t-594c8a5ffbc6260b6a79f03e5911578de1a74bc41a3337aa0a2181c79b3e91693</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/PMC3252368/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252368/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22241991$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kuhn, Richard J.</contributor><creatorcontrib>Pham, Alissa M</creatorcontrib><creatorcontrib>Langlois, Ryan A</creatorcontrib><creatorcontrib>TenOever, Benjamin R</creatorcontrib><title>Replication in cells of hematopoietic origin is necessary for Dengue virus dissemination</title><title>PLoS pathogens</title><addtitle>PLoS Pathog</addtitle><description>Dengue virus (DENV) is a mosquito-borne pathogen for which no vaccine or specific therapeutic is available. Although it is well established that dendritic cells and macrophages are primary sites of DENV replication, it remains unclear whether non-hematopoietic cellular compartments serve as virus reservoirs. Here, we exploited hematopoietic-specific microRNA-142 (miR-142) to control virus tropism by inserting tandem target sites into the virus to restrict replication exclusively in this cell population. In vivo use of this virus restricted infection of CD11b+, CD11c+, and CD45+ cells, resulting in a loss of virus spread, regardless of the route of administration. Furthermore, sequencing of the targeted virus population that persisted at low levels, demonstrated total excision of the inserted miR-142 target sites. The complete conversion of the virus population under these selective conditions suggests that these immune cells are the predominant sources of virus amplification. Taken together, this work highlights the importance of hematopoietic cells for DENV replication and showcases an invaluable tool for the study of virus pathogenesis.</description><subject>Animals</subject><subject>Antigens, CD - genetics</subject><subject>Antigens, CD - immunology</subject><subject>Antigens, CD - metabolism</subject><subject>Biology</subject><subject>Bone marrow cells</subject><subject>Cloning</subject><subject>Dengue - genetics</subject><subject>Dengue - immunology</subject><subject>Dengue - metabolism</subject><subject>Dengue fever</subject><subject>Dengue virus</subject><subject>Dengue Virus - physiology</subject><subject>Dengue viruses</subject><subject>Distribution</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Health aspects</subject><subject>HEK293 Cells</subject><subject>Hematopoietic Stem Cells - immunology</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>Hematopoietic Stem Cells - virology</subject><subject>Heparan sulfate</subject><subject>Humans</subject><subject>Infections</subject><subject>Lymphatic system</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - immunology</subject><subject>MicroRNAs - metabolism</subject><subject>Mutation</subject><subject>Pathogenesis</subject><subject>Physiological aspects</subject><subject>Population</subject><subject>Proteins</subject><subject>Virus Replication - physiology</subject><subject>Viruses</subject><issn>1553-7374</issn><issn>1553-7366</issn><issn>1553-7374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqVk99r1TAUx4sobk7_A9GCD-LDvSZN0iQvwpi_LgyFqeBbOE1Pu4zepkvaof-96W43dmUgkoeE5HO-OeebnCx7TsmaMknfXvgp9NCthwHGNSWk4KV4kB1SIdhKMskf3lkfZE9ivCCEU0bLx9lBURScak0Ps59nOHTOwuh8n7s-t9h1MfdNfo5bGP3gHY7O5j64Np26mPdoMUYIv_PGh_w99u2E-ZULU8xrFyNuXX8t9jR71EAX8dkyH2U_Pn74fvJ5dfr10-bk-HRlS12MK6G5VSCaprJlUZKqBKkbwlBoSoVUNVKQvLKcAmNMAhAoqKJW6oqhpqVmR9nLne7Q-WgWU6KhhdLJFCJJIjY7ovZwYYbgtil748GZ6w0fWgMhFdmh0dQqqWldzXZypaBSDfBGabACa2RJ691y21RtsbbYjwG6PdH9k96dm9ZfGVaIgpUqCbxeBIK_nDCOZuvibDr06KdotOAl01qX_yZpSQWRYi7w1V_k_TYsVAupUtc3PiVoZ01zXKjEcCXn_Nb3UGnU6WWt77FxaX8v4M1eQGJG_DW2MMVoNt_O_oP9ss_yHWuDjzFgc2syJWZugJsizdwAZmmAFPbi7gPdBt38ePYHQf4AxA</recordid><startdate>20120101</startdate><enddate>20120101</enddate><creator>Pham, Alissa M</creator><creator>Langlois, Ryan A</creator><creator>TenOever, Benjamin 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>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>F1W</scope><scope>H95</scope><scope>H97</scope><scope>L.G</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20120101</creationdate><title>Replication in cells of hematopoietic origin is necessary for Dengue virus dissemination</title><author>Pham, Alissa M ; Langlois, Ryan A ; TenOever, Benjamin R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-594c8a5ffbc6260b6a79f03e5911578de1a74bc41a3337aa0a2181c79b3e91693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Antigens, CD - genetics</topic><topic>Antigens, CD - immunology</topic><topic>Antigens, CD - metabolism</topic><topic>Biology</topic><topic>Bone marrow cells</topic><topic>Cloning</topic><topic>Dengue - genetics</topic><topic>Dengue - immunology</topic><topic>Dengue - metabolism</topic><topic>Dengue fever</topic><topic>Dengue virus</topic><topic>Dengue Virus - physiology</topic><topic>Dengue viruses</topic><topic>Distribution</topic><topic>Genetic aspects</topic><topic>Genomes</topic><topic>Health aspects</topic><topic>HEK293 Cells</topic><topic>Hematopoietic Stem Cells - immunology</topic><topic>Hematopoietic Stem Cells - metabolism</topic><topic>Hematopoietic Stem Cells - virology</topic><topic>Heparan sulfate</topic><topic>Humans</topic><topic>Infections</topic><topic>Lymphatic system</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - immunology</topic><topic>MicroRNAs - metabolism</topic><topic>Mutation</topic><topic>Pathogenesis</topic><topic>Physiological aspects</topic><topic>Population</topic><topic>Proteins</topic><topic>Virus Replication - physiology</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pham, Alissa M</creatorcontrib><creatorcontrib>Langlois, Ryan A</creatorcontrib><creatorcontrib>TenOever, Benjamin R</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: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</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>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS pathogens</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pham, Alissa M</au><au>Langlois, Ryan A</au><au>TenOever, Benjamin R</au><au>Kuhn, Richard J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Replication in cells of hematopoietic origin is necessary for Dengue virus dissemination</atitle><jtitle>PLoS pathogens</jtitle><addtitle>PLoS Pathog</addtitle><date>2012-01-01</date><risdate>2012</risdate><volume>8</volume><issue>1</issue><spage>e1002465</spage><epage>e1002465</epage><pages>e1002465-e1002465</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>Dengue virus (DENV) is a mosquito-borne pathogen for which no vaccine or specific therapeutic is available. Although it is well established that dendritic cells and macrophages are primary sites of DENV replication, it remains unclear whether non-hematopoietic cellular compartments serve as virus reservoirs. Here, we exploited hematopoietic-specific microRNA-142 (miR-142) to control virus tropism by inserting tandem target sites into the virus to restrict replication exclusively in this cell population. In vivo use of this virus restricted infection of CD11b+, CD11c+, and CD45+ cells, resulting in a loss of virus spread, regardless of the route of administration. Furthermore, sequencing of the targeted virus population that persisted at low levels, demonstrated total excision of the inserted miR-142 target sites. The complete conversion of the virus population under these selective conditions suggests that these immune cells are the predominant sources of virus amplification. Taken together, this work highlights the importance of hematopoietic cells for DENV replication and showcases an invaluable tool for the study of virus pathogenesis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22241991</pmid><doi>10.1371/journal.ppat.1002465</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1553-7374 |
| ispartof | PLoS pathogens, 2012-01, Vol.8 (1), p.e1002465-e1002465 |
| issn | 1553-7374 1553-7366 1553-7374 |
| language | eng |
| recordid | cdi_plos_journals_1289100070 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | Animals Antigens, CD - genetics Antigens, CD - immunology Antigens, CD - metabolism Biology Bone marrow cells Cloning Dengue - genetics Dengue - immunology Dengue - metabolism Dengue fever Dengue virus Dengue Virus - physiology Dengue viruses Distribution Genetic aspects Genomes Health aspects HEK293 Cells Hematopoietic Stem Cells - immunology Hematopoietic Stem Cells - metabolism Hematopoietic Stem Cells - virology Heparan sulfate Humans Infections Lymphatic system Mice Mice, Knockout MicroRNAs - genetics MicroRNAs - immunology MicroRNAs - metabolism Mutation Pathogenesis Physiological aspects Population Proteins Virus Replication - physiology Viruses |
| title | Replication in cells of hematopoietic origin is necessary for Dengue virus dissemination |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-29T20%3A01%3A30IST&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=Replication%20in%20cells%20of%20hematopoietic%20origin%20is%20necessary%20for%20Dengue%20virus%20dissemination&rft.jtitle=PLoS%20pathogens&rft.au=Pham,%20Alissa%20M&rft.date=2012-01-01&rft.volume=8&rft.issue=1&rft.spage=e1002465&rft.epage=e1002465&rft.pages=e1002465-e1002465&rft.issn=1553-7374&rft.eissn=1553-7374&rft_id=info:doi/10.1371/journal.ppat.1002465&rft_dat=%3Cgale_plos_%3EA280004878%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=1289100070&rft_id=info:pmid/22241991&rft_galeid=A280004878&rft_doaj_id=oai_doaj_org_article_91c8791db0024488ab8fa4f89ac5ede3&rfr_iscdi=true |