Outcomes of Congenital Zika Disease Depend on Timing of Infection and Maternal-Fetal Interferon Action
Summary: Zika virus (ZIKV) infection during pregnancy in humans results in intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we found that fetus-derived type I interferon (IFN-I) signaling can enhance anti-ZIKV responses and provide clinical benefits to the fetus. Becaus...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-11-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717315073 |
| _version_ | 1818944772228775936 |
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| author | Jinling Chen Yuejin Liang Panpan Yi Lanman Xu Hal K. Hawkins Shannan L. Rossi Lynn Soong Jiyang Cai Ramkumar Menon Jiaren Sun |
| author_facet | Jinling Chen Yuejin Liang Panpan Yi Lanman Xu Hal K. Hawkins Shannan L. Rossi Lynn Soong Jiyang Cai Ramkumar Menon Jiaren Sun |
| author_sort | Jinling Chen |
| collection | DOAJ |
| description | Summary: Zika virus (ZIKV) infection during pregnancy in humans results in intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we found that fetus-derived type I interferon (IFN-I) signaling can enhance anti-ZIKV responses and provide clinical benefits to the fetus. Because IFN-λ shares signaling cascades and antiviral functions with IFN-I, we investigated the in vivo effects of IFN-λ in ZIKV-infected pregnant mice. IFN-λ administration during mid-pregnancy reduced ZIKV burden in maternal and fetal organs and alleviated placental injuries and fetal demise. In addition, prophylactic and therapeutic treatment of IFN-λ1 in a human trophoblast line, as well as in primary human amniotic epithelial cells, greatly reduced the ZIKV burden. Our data highlight IFN-λ1 as a potential therapeutic useful for women at risk for congenital Zika disease. : Chen et al. find that fetus-derived IFN-I signaling contributes to anti-ZIKV responses. IFN-λ administration during mid-pregnancy promotes host defense and reduces disease severity. IFN-λ1 treatment upregulates MX1 expression and establishes an antiviral state, leading to reduced ZIKV replication or elimination. Keywords: Zika virus, congenital infection, interferon-λ, antiviral, animal model, human pregnancy, gestational stage |
| first_indexed | 2024-12-20T07:48:32Z |
| format | Article |
| id | doaj.art-348c0282574641caaea5eb73590cc253 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-20T07:48:32Z |
| publishDate | 2017-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-348c0282574641caaea5eb73590cc2532022-12-21T19:47:54ZengElsevierCell Reports2211-12472017-11-0121615881599Outcomes of Congenital Zika Disease Depend on Timing of Infection and Maternal-Fetal Interferon ActionJinling Chen0Yuejin Liang1Panpan Yi2Lanman Xu3Hal K. Hawkins4Shannan L. Rossi5Lynn Soong6Jiyang Cai7Ramkumar Menon8Jiaren Sun9Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu 226001, China, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha, Hunan 410008, ChinaDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Infectious Diseases, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, ChinaDepartment of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA; Corresponding authorSummary: Zika virus (ZIKV) infection during pregnancy in humans results in intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we found that fetus-derived type I interferon (IFN-I) signaling can enhance anti-ZIKV responses and provide clinical benefits to the fetus. Because IFN-λ shares signaling cascades and antiviral functions with IFN-I, we investigated the in vivo effects of IFN-λ in ZIKV-infected pregnant mice. IFN-λ administration during mid-pregnancy reduced ZIKV burden in maternal and fetal organs and alleviated placental injuries and fetal demise. In addition, prophylactic and therapeutic treatment of IFN-λ1 in a human trophoblast line, as well as in primary human amniotic epithelial cells, greatly reduced the ZIKV burden. Our data highlight IFN-λ1 as a potential therapeutic useful for women at risk for congenital Zika disease. : Chen et al. find that fetus-derived IFN-I signaling contributes to anti-ZIKV responses. IFN-λ administration during mid-pregnancy promotes host defense and reduces disease severity. IFN-λ1 treatment upregulates MX1 expression and establishes an antiviral state, leading to reduced ZIKV replication or elimination. Keywords: Zika virus, congenital infection, interferon-λ, antiviral, animal model, human pregnancy, gestational stagehttp://www.sciencedirect.com/science/article/pii/S2211124717315073 |
| spellingShingle | Jinling Chen Yuejin Liang Panpan Yi Lanman Xu Hal K. Hawkins Shannan L. Rossi Lynn Soong Jiyang Cai Ramkumar Menon Jiaren Sun Outcomes of Congenital Zika Disease Depend on Timing of Infection and Maternal-Fetal Interferon Action Cell Reports |
| title | Outcomes of Congenital Zika Disease Depend on Timing of Infection and Maternal-Fetal Interferon Action |
| title_full | Outcomes of Congenital Zika Disease Depend on Timing of Infection and Maternal-Fetal Interferon Action |
| title_fullStr | Outcomes of Congenital Zika Disease Depend on Timing of Infection and Maternal-Fetal Interferon Action |
| title_full_unstemmed | Outcomes of Congenital Zika Disease Depend on Timing of Infection and Maternal-Fetal Interferon Action |
| title_short | Outcomes of Congenital Zika Disease Depend on Timing of Infection and Maternal-Fetal Interferon Action |
| title_sort | outcomes of congenital zika disease depend on timing of infection and maternal fetal interferon action |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717315073 |
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