Primary Human Placental Trophoblasts are Permissive for Zika Virus (ZIKV) Replication
Zika virus (ZIKV) is an emerging mosquito-borne ( Aedes genus) arbovirus of the Flaviviridae family. Although ZIKV has been predominately associated with a mild or asymptomatic dengue-like disease, its appearance in the Americas has been accompanied by a multi-fold increase in reported incidence of...
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| Veröffentlicht in: | Scientific reports 2017-01, Vol.7 (1), p.41389-41389, Article 41389 |
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| creator | Aagaard, Kjersti M. Lahon, Anismrita Suter, Melissa A. Arya, Ravi P. Seferovic, Maxim D. Vogt, Megan B. Hu, Min Stossi, Fabio Mancini, Michael A. Harris, R. Alan Kahr, Maike Eppes, Catherine Rac, Martha Belfort, Michael A. Park, Chun Shik Lacorazza, Daniel Rico-Hesse, Rebecca |
| description | Zika virus (ZIKV) is an emerging mosquito-borne (
Aedes
genus) arbovirus of the
Flaviviridae
family. Although ZIKV has been predominately associated with a mild or asymptomatic dengue-like disease, its appearance in the Americas has been accompanied by a multi-fold increase in reported incidence of fetal microcephaly and brain malformations. The source and mode of vertical transmission from mother to fetus is presumptively transplacental, although a causal link explaining the interval delay between maternal symptoms and observed fetal malformations following infection has been missing. In this study, we show that primary human placental trophoblasts from non-exposed donors (
n
= 20) can be infected by primary passage ZIKV-FLR isolate, and uniquely allowed for ZIKV viral RNA replication when compared to dengue virus (DENV). Consistent with their being permissive for ZIKV infection, primary trophoblasts expressed multiple putative ZIKV cell entry receptors, and cellular function and differentiation were preserved. These findings suggest that ZIKV-FLR strain can replicate in human placental trophoblasts without host cell destruction, thereby serving as a likely permissive reservoir and portal of fetal transmission with risk of latent microcephaly and malformations. |
| doi_str_mv | 10.1038/srep41389 |
| format | Article |
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Aedes
genus) arbovirus of the
Flaviviridae
family. Although ZIKV has been predominately associated with a mild or asymptomatic dengue-like disease, its appearance in the Americas has been accompanied by a multi-fold increase in reported incidence of fetal microcephaly and brain malformations. The source and mode of vertical transmission from mother to fetus is presumptively transplacental, although a causal link explaining the interval delay between maternal symptoms and observed fetal malformations following infection has been missing. In this study, we show that primary human placental trophoblasts from non-exposed donors (
n
= 20) can be infected by primary passage ZIKV-FLR isolate, and uniquely allowed for ZIKV viral RNA replication when compared to dengue virus (DENV). Consistent with their being permissive for ZIKV infection, primary trophoblasts expressed multiple putative ZIKV cell entry receptors, and cellular function and differentiation were preserved. These findings suggest that ZIKV-FLR strain can replicate in human placental trophoblasts without host cell destruction, thereby serving as a likely permissive reservoir and portal of fetal transmission with risk of latent microcephaly and malformations.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep41389</identifier><identifier>PMID: 28128342</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/106 ; 14/32 ; 631/326/596/2563 ; 692/420/254 ; Adult ; Aquatic insects ; Cells, Cultured ; Dengue - pathology ; Dengue - virology ; Dengue fever ; Dengue Virus - physiology ; Female ; Flavivirus ; Giant Cells - metabolism ; Giant Cells - pathology ; Humanities and Social Sciences ; Humans ; Ligands ; Microcephaly ; Microencephaly ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Mosquitoes ; multidisciplinary ; Phylogeny ; Placenta - pathology ; Pregnancy ; Receptors, Virus - metabolism ; RNA, Viral - metabolism ; Science ; Science (multidisciplinary) ; Toll-Like Receptors - metabolism ; Trophoblasts - virology ; Vector-borne diseases ; Virology ; Virus Replication - physiology ; Zika virus ; Zika Virus - physiology ; Zika Virus Infection - pathology ; Zika Virus Infection - virology</subject><ispartof>Scientific reports, 2017-01, Vol.7 (1), p.41389-41389, Article 41389</ispartof><rights>The Author(s) 2017</rights><rights>Copyright Nature Publishing Group Feb 2017</rights><rights>Copyright © 2017, The Author(s) 2017 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-fb6a3dc1cef14860df2a94ed6f9ea9f1747294a38b595ea33a8cf6ad0d3f29853</citedby><cites>FETCH-LOGICAL-c504t-fb6a3dc1cef14860df2a94ed6f9ea9f1747294a38b595ea33a8cf6ad0d3f29853</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/PMC5269613/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5269613/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28128342$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aagaard, Kjersti M.</creatorcontrib><creatorcontrib>Lahon, Anismrita</creatorcontrib><creatorcontrib>Suter, Melissa A.</creatorcontrib><creatorcontrib>Arya, Ravi P.</creatorcontrib><creatorcontrib>Seferovic, Maxim D.</creatorcontrib><creatorcontrib>Vogt, Megan B.</creatorcontrib><creatorcontrib>Hu, Min</creatorcontrib><creatorcontrib>Stossi, Fabio</creatorcontrib><creatorcontrib>Mancini, Michael A.</creatorcontrib><creatorcontrib>Harris, R. Alan</creatorcontrib><creatorcontrib>Kahr, Maike</creatorcontrib><creatorcontrib>Eppes, Catherine</creatorcontrib><creatorcontrib>Rac, Martha</creatorcontrib><creatorcontrib>Belfort, Michael A.</creatorcontrib><creatorcontrib>Park, Chun Shik</creatorcontrib><creatorcontrib>Lacorazza, Daniel</creatorcontrib><creatorcontrib>Rico-Hesse, Rebecca</creatorcontrib><title>Primary Human Placental Trophoblasts are Permissive for Zika Virus (ZIKV) Replication</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Zika virus (ZIKV) is an emerging mosquito-borne (
Aedes
genus) arbovirus of the
Flaviviridae
family. Although ZIKV has been predominately associated with a mild or asymptomatic dengue-like disease, its appearance in the Americas has been accompanied by a multi-fold increase in reported incidence of fetal microcephaly and brain malformations. The source and mode of vertical transmission from mother to fetus is presumptively transplacental, although a causal link explaining the interval delay between maternal symptoms and observed fetal malformations following infection has been missing. In this study, we show that primary human placental trophoblasts from non-exposed donors (
n
= 20) can be infected by primary passage ZIKV-FLR isolate, and uniquely allowed for ZIKV viral RNA replication when compared to dengue virus (DENV). Consistent with their being permissive for ZIKV infection, primary trophoblasts expressed multiple putative ZIKV cell entry receptors, and cellular function and differentiation were preserved. These findings suggest that ZIKV-FLR strain can replicate in human placental trophoblasts without host cell destruction, thereby serving as a likely permissive reservoir and portal of fetal transmission with risk of latent microcephaly and malformations.</description><subject>13/106</subject><subject>14/32</subject><subject>631/326/596/2563</subject><subject>692/420/254</subject><subject>Adult</subject><subject>Aquatic insects</subject><subject>Cells, Cultured</subject><subject>Dengue - pathology</subject><subject>Dengue - virology</subject><subject>Dengue fever</subject><subject>Dengue Virus - physiology</subject><subject>Female</subject><subject>Flavivirus</subject><subject>Giant Cells - metabolism</subject><subject>Giant Cells - pathology</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Ligands</subject><subject>Microcephaly</subject><subject>Microencephaly</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Mosquitoes</subject><subject>multidisciplinary</subject><subject>Phylogeny</subject><subject>Placenta - pathology</subject><subject>Pregnancy</subject><subject>Receptors, Virus - metabolism</subject><subject>RNA, Viral - metabolism</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Toll-Like Receptors - metabolism</subject><subject>Trophoblasts - virology</subject><subject>Vector-borne diseases</subject><subject>Virology</subject><subject>Virus Replication - physiology</subject><subject>Zika virus</subject><subject>Zika Virus - physiology</subject><subject>Zika Virus Infection - pathology</subject><subject>Zika Virus Infection - virology</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNplkUtLAzEUhYMoVtSFf0ACbqxQnTxmJtkIIr5QsIh20U24nUlqdDoZkxnBf29Ka6mazQ3cj3PP4SB0QJJTkjBxFrxuOGFCbqAdmvB0QBmlm2v_HtoP4S2JL6WSE7mNelQQKhinO-hl6O0M_Be-7WZQ42EFha5bqPCzd82rm1QQ2oDBazzUfmZDsJ8aG-fx2L4DHlnfBXw8vrsf9fGTbipbQGtdvYe2DFRB7y_nLnq5vnq-vB08PN7cXV48DIo04e3ATDJgZUEKbQgXWVIaCpLrMjNSgzQk53l0DExMUplqYAxEYTIok5IZKkXKdtH5QrfpJjNdzq17qFSzyKQcWPV7U9tXNXWfKqWZzAiLAsdLAe8-Oh1aFTMWuqqg1q4LioiM5lkuiYzo0R_0zXW-jvEiJSXPGUlFpPoLqvAuxGrMygxJ1Lwvteorsofr7lfkTzsROFkAIa7qqfZrJ_-pfQPZo5-8</recordid><startdate>20170127</startdate><enddate>20170127</enddate><creator>Aagaard, Kjersti M.</creator><creator>Lahon, Anismrita</creator><creator>Suter, Melissa A.</creator><creator>Arya, Ravi P.</creator><creator>Seferovic, Maxim D.</creator><creator>Vogt, Megan B.</creator><creator>Hu, Min</creator><creator>Stossi, Fabio</creator><creator>Mancini, Michael A.</creator><creator>Harris, R. 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Alan</creatorcontrib><creatorcontrib>Kahr, Maike</creatorcontrib><creatorcontrib>Eppes, Catherine</creatorcontrib><creatorcontrib>Rac, Martha</creatorcontrib><creatorcontrib>Belfort, Michael A.</creatorcontrib><creatorcontrib>Park, Chun Shik</creatorcontrib><creatorcontrib>Lacorazza, Daniel</creatorcontrib><creatorcontrib>Rico-Hesse, Rebecca</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science 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>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>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>Science 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 Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aagaard, Kjersti M.</au><au>Lahon, Anismrita</au><au>Suter, Melissa A.</au><au>Arya, Ravi P.</au><au>Seferovic, Maxim D.</au><au>Vogt, Megan B.</au><au>Hu, Min</au><au>Stossi, Fabio</au><au>Mancini, Michael A.</au><au>Harris, R. Alan</au><au>Kahr, Maike</au><au>Eppes, Catherine</au><au>Rac, Martha</au><au>Belfort, Michael A.</au><au>Park, Chun Shik</au><au>Lacorazza, Daniel</au><au>Rico-Hesse, Rebecca</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Primary Human Placental Trophoblasts are Permissive for Zika Virus (ZIKV) Replication</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2017-01-27</date><risdate>2017</risdate><volume>7</volume><issue>1</issue><spage>41389</spage><epage>41389</epage><pages>41389-41389</pages><artnum>41389</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Zika virus (ZIKV) is an emerging mosquito-borne (
Aedes
genus) arbovirus of the
Flaviviridae
family. Although ZIKV has been predominately associated with a mild or asymptomatic dengue-like disease, its appearance in the Americas has been accompanied by a multi-fold increase in reported incidence of fetal microcephaly and brain malformations. The source and mode of vertical transmission from mother to fetus is presumptively transplacental, although a causal link explaining the interval delay between maternal symptoms and observed fetal malformations following infection has been missing. In this study, we show that primary human placental trophoblasts from non-exposed donors (
n
= 20) can be infected by primary passage ZIKV-FLR isolate, and uniquely allowed for ZIKV viral RNA replication when compared to dengue virus (DENV). Consistent with their being permissive for ZIKV infection, primary trophoblasts expressed multiple putative ZIKV cell entry receptors, and cellular function and differentiation were preserved. These findings suggest that ZIKV-FLR strain can replicate in human placental trophoblasts without host cell destruction, thereby serving as a likely permissive reservoir and portal of fetal transmission with risk of latent microcephaly and malformations.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>28128342</pmid><doi>10.1038/srep41389</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Scientific reports, 2017-01, Vol.7 (1), p.41389-41389, Article 41389 |
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| subjects | 13/106 14/32 631/326/596/2563 692/420/254 Adult Aquatic insects Cells, Cultured Dengue - pathology Dengue - virology Dengue fever Dengue Virus - physiology Female Flavivirus Giant Cells - metabolism Giant Cells - pathology Humanities and Social Sciences Humans Ligands Microcephaly Microencephaly MicroRNAs - genetics MicroRNAs - metabolism Mosquitoes multidisciplinary Phylogeny Placenta - pathology Pregnancy Receptors, Virus - metabolism RNA, Viral - metabolism Science Science (multidisciplinary) Toll-Like Receptors - metabolism Trophoblasts - virology Vector-borne diseases Virology Virus Replication - physiology Zika virus Zika Virus - physiology Zika Virus Infection - pathology Zika Virus Infection - virology |
| title | Primary Human Placental Trophoblasts are Permissive for Zika Virus (ZIKV) Replication |
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