Outcomes of Congenital Zika Disease Depend on Timing of Infection and Maternal-Fetal Interferon Action
Jinling Chen,
Yuejin Liang,
Panpan Yi,
Lanman Xu,
Hal K. Hawkins,
Shannan L. Rossi,
Lynn Soong,
Jiyang Cai,
Ramkumar Menon,
Jiaren Sun
Affiliations
Jinling Chen
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
Yuejin Liang
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
Panpan Yi
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
Lanman Xu
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
Hal K. Hawkins
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA
Shannan L. Rossi
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
Lynn Soong
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
Jiyang Cai
Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA
Ramkumar Menon
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX 77555, USA
Jiaren Sun
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; Corresponding author
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
