Jinling Chen1, Yuejin Liang2, Panpan Yi3, Lanman Xu4, Hal K Hawkins5, Shannan L Rossi6, Lynn Soong7, Jiyang Cai8, Ramkumar Menon9, Jiaren Sun10. 1. Department 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, USA. 2. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA. 3. Department 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, China. 4. Department 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, China. 5. Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA. 6. Department 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, USA. 7. Department 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. 8. Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA. 9. Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX 77555, USA. 10. Department 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. Electronic address: jisun@utmb.edu.
Abstract
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.
pan class="Species">Zika virus (pan class="Species">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.
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