Dengue and Zika Virus Cross-Reactive Human Monoclonal Antibodies Protect against Spondweni Virus Infection and Pathogenesis in Mice

Publication date: 5 February 2019Source: Cell Reports, Volume 26, Issue 6Author(s): Vanessa Salazar, Brett W. Jagger, Juthathip Mongkolsapaya, Katherine E. Burgomaster, Wanwisa Dejnirattisai, Emma S. Winkler, Estefania Fernandez, Christopher A. Nelson, Daved H. Fremont, Theodore C. Pierson, James E. Crowe, Gavin R. Screaton, Michael S. DiamondSummarySpondweni virus (SPOV) is the flavivirus that is most closely related to Zika virus (ZIKV). Although SPOV causes sporadic human infections in Africa, recently it was found in Culex mosquitoes in Haiti. To investigate the pathogenic spectrum of SPOV, we developed infection models in mice. Although two SPOV strains failed to cause disease in immunocompetent mice, each accumulated in the brain, spleen, eye, testis, and kidney when type I interferon signaling was blocked and unexpectedly caused infection, immune cell infiltration, and swelling in the ankle. In pregnant mice, SPOV replicated in the placenta and fetus but did not cause placental insufficiency or microcephaly. We identified human antibodies from ZIKV or DENV immune subjects that neutralized SPOV infection and protected against lethal challenge. Our experiments describe similarities and differences in clinical syndromes between SPOV and ZIKV and suggest that their serological relatedness has implications for antibody therapeutics and flavivirus vaccine development.Graphical Abstract

Source: Cell Reports - February 6, 2019 Category: Cytology Source Type: research