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

Abstract

Summary: Spondweni 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. : Salazar et al. show that SPOV, the flavivirus most closely related to ZIKV, infects mice when type I interferon signaling is blocked. SPOV causes ankle swelling and infection in the foot, which is more typical of alphaviruses. Human antibodies from ZIKV or DENV subjects protect against lethal SPOV challenge. Keywords: flavivirus, pathogenesis, Spondweni virus, Zika virus, Dengue virus, arthritis, antibody therapy, immunity