Intraperitoneal injection with dengue virus type 1-infected K562 cells results in complete fatality among immunocompetent mice

Abstract

Dengue is one of the most important mosquito-borne viral diseases. Over half of the world's population is living in dengue endemic countries, where 100 million cases are estimated to occur annually. Although one dengue vaccine is currently available commercially, unfortunately its safety and efficacy has not been demonstrated for seronegative populations. Therefore, other vaccine candidates as well as antivirals are urgently required to control dengue diseases. To contribute to the development of preventative measures, in the present study we established an immunocompetent-mouse infection model using dengue virus type 1 Mochizuki strain. Following intraperitoneal injection with K562 cells infected with Mochizuki strain, all mice injected with ≥1 × 106 cells were killed within 7–11 days. Mice injected with ≥1 × 107 cells showed viremia (~104–105 FFU/ml) within 24 h of injection. Since a higher infective titer was detected in the mouse brain, this suggested that viruses were transmitted from the blood circulation into the brain. In further experiments, mice immunized with two types of DNA vaccines were challenged with virus. In contrast to the non-immunized control mice, all vaccinated mice survived after challenge. This immunocompetent-mouse infection model using dengue virus type 1 Mochizuki strain may be a useful tool to evaluate vaccines and preventive medicines against dengue virus.