Altered vector competence in an experimental mosquito-mouse transmission model of Zika infection

Few animal models of Zika virus (ZIKV) infection have incorporated arthropod-borne transmission. Here, we establish an Aedes aegypti mosquito model of ZIKV infection of mice, and demonstrate altered vector competency among three strains, (Orlando, ORL, Ho Chi Minh, HCM, and Patilas, PAT). All strains acquired ZIKV in their midguts after a blood meal from infected mice, but ZIKV transmission only occurred in mice fed upon by HCM, and to a lesser extent PAT, but not ORL, mosquitoes. This defect in transmission from ORL or PAT mosquitoes was overcome by intrathoracic injection of ZIKV into mosquito. Genetic analysis revealed significant diversity among these strains, suggesting a genetic basis for differences in ability for mosquito strains to transmit ZIKV. The intrathoracic injection mosquito-mouse transmission model is critical to understanding the influence of mosquitoes on ZIKV transmission, infectivity and pathogenesis in the vertebrate host, and represents a natural transmission route for testing vaccines and therapeutics.Author summary: Zika virus (ZIKV), an emerging flavivirus, is associated with severe clinical outcomes, including Guillain-Barre syndrome and birth defects. Transmission of ZIKV is primarily mosquito-borne, but the complete transmission cycle from mammalian host to mosquito and back to mammalian host has not yet been demonstrated experimentally. Here, for the first time, we establish a transmission model of ZIKV between mice lacking both interferon α and interferon γ receptor (AG129) and the Aedes aegypti mosquito, the main vector of ZIKV. We also highlight differences in vector competence among a common laboratory strain, Orlando (ORL), and two wild-caught strains, Ho Chi Minh (HCM) and Patillas (PAT), of the Aedes aegypti mosquito using oral feeding on infected mice and intrathoracic inoculation of ZIKV. Our results suggest different ZIKV susceptibility among these strains, which could be relevant as this virus spreads throughout the globe. In addition, the mosquito transmission model demonstrated here can be used to better understand the effect mosquitoes have on replication and pathogenesis of this virus.