{"corpus_id":73452588,"paper_sha":"61a831b93752544ca8cb56d5c62da718b91d7483","doi":"10.1016/j.immuni.2019.01.005","arxiv_id":null,"pmid":30737148,"pmcid":"PMC6947917","mag_id":2911726030,"dblp_id":null,"acl_id":null,"title":"Dengue Virus Immunity Increases Zika Virus‐Induced Damage during Pregnancy","year":2019,"publication_date":"2019-03-01","venue":"Immunity","journal":{"name":"Immunity","pages":"751–762,762.e1–762.e5","volume":"50"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, N.I.H., Extramural"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":67,"citation_count":89,"influential_citation_count":7,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Antibodies, Monoclonal","mj":false,"qs":[{"q":"immunology","mj":false,"ui":"Q000276"}],"ui":"D000911"},{"d":"Antibodies, Neutralizing","mj":false,"qs":[{"q":"immunology","mj":false,"ui":"Q000276"}],"ui":"D057134"},{"d":"Antibodies, Viral","mj":false,"qs":[{"q":"immunology","mj":false,"ui":"Q000276"}],"ui":"D000914"},{"d":"Antibody-Dependent Enhancement","mj":false,"qs":[{"q":"immunology","mj":false,"ui":"Q000276"}],"ui":"D019067"},{"d":"Cell Line, Tumor","mj":false,"ui":"D045744"},{"d":"Chlorocebus aethiops","mj":false,"ui":"D002522"},{"d":"Cross Reactions","mj":false,"qs":[{"q":"immunology","mj":false,"ui":"Q000276"}],"ui":"D003429"},{"d":"Dengue Virus","mj":false,"qs":[{"q":"immunology","mj":true,"ui":"Q000276"}],"ui":"D003716"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Immunity","mj":false,"qs":[{"q":"immunology","mj":true,"ui":"Q000276"}],"ui":"D007109"},{"d":"K562 Cells","mj":false,"ui":"D020014"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"Pregnancy","mj":false,"ui":"D011247"},{"d":"Vero Cells","mj":false,"ui":"D014709"},{"d":"Zika Virus","mj":false,"qs":[{"q":"immunology","mj":true,"ui":"Q000276"}],"ui":"D000071244"},{"d":"Zika Virus Infection","mj":false,"qs":[{"q":"immunology","mj":true,"ui":"Q000276"}],"ui":"D000071243"}],"chemicals":[{"n":"Antibodies, Monoclonal","ui":"D000911","reg":"0"},{"n":"Antibodies, Neutralizing","ui":"D057134","reg":"0"},{"n":"Antibodies, Viral","ui":"D000914","reg":"0"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"http://www.cell.com/article/S1074761319300287/pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/61a831b93752544ca8cb56d5c62da718b91d7483","s2_open_access_license":"publisher-specific-oa","s2_open_access_status":"BRONZE","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"&NA; Zika virus (ZIKV) has recently been associated with birth defects and pregnancy loss after maternal infection. Because dengue virus (DENV) and ZIKV co‐circulate, understanding the role of antibody‐dependent enhancement in the context of pregnancy is critical. Here, we showed that the presence of DENV‐specific antibodies in ZIKV‐infected pregnant mice significantly increased placental damage, fetal growth restriction, and fetal resorption. This was associated with enhanced viral replication in the placenta that coincided with an increased frequency of infected trophoblasts. ZIKV‐infected human placental tissues also showed increased replication in the presence of DENV antibodies, which was reversed by Fc&ggr;R blocking antibodies. Furthermore, ZIKV‐mediated fetal pathogenesis was enhanced in mice in the presence of a DENV‐reactive monoclonal antibody, but not in the presence of the LALA variant, indicating a dependence on Fc&ggr;R engagement. Our data suggest a possible mechanism for the recent increase in severe pregnancy outcomes after ZIKV infection in DENV‐endemic areas. HighlightsDengue‐specific antibodies can enhance Zika virus pathogenesis during pregnancyEnhancement of Zika pathogenesis was observed in the placenta, not in the fetusPlacental damage was associated with an increase in infected trophoblastsThis process was found to be Fc&ggr;R mediated","claims":[{"public_id":"cl_addac5a5566776b92d537ac46b3992fe","status":"active","text":"A dengue virus-reactive monoclonal antibody enhances Zika virus-mediated fetal pathogenesis in mice, but its Fc-null LALA variant does not, indicating that enhancement depends on FcγR engagement.","confidence":0.88,"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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pathogenesis in the presence of dengue antibodies coincides with increased placental viral replication and a higher frequency of infected trophoblasts.","confidence":0.85,"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_9095405b0b50e896b6c77d061f09dd8e"},{"public_id":"cl_b2a113fa0e8775805a6e476f9ed83a98","status":"active","text":"Zika virus replication is increased in human placental tissue in the presence of dengue virus antibodies, and this enhancement is reversed by FcγR blocking antibodies.","confidence":0.85,"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_b2a113fa0e8775805a6e476f9ed83a98"}],"concepts":[{"public_id":"co_0342dc04054c2f3e1b2f434ed4de99b3","status":"active","name":"DENV-reactive monoclonal antibody","description":"A monoclonal antibody reactive to dengue virus used to test enhancement of Zika pathogenesis in mice.","types":["reagent"],"aliases":[],"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":2,"public_id":"4715169a40","public_label":"AK 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