Fundación INFANT Buenos Aires Argentina.
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) Buenos Aires Argentina.
Animal Model Exp Med. 2020 Dec 21;4(1):16-26. doi: 10.1002/ame2.12145. eCollection 2021 Mar.
Dengue is a significant public health concern across tropical and subtropical regions worldwide, principally causing disease in children. Very young children are at increased risk of severe manifestations of dengue infection. The mechanism of dengue disease in this population is not fully understood. In this study, we present a murine model of dengue virus primary infection in suckling C57BL/6 and BALB/c mice in order to investigate disease pathogenesis. Three-day-old C57BL/6 mice intraperitoneally infected with DENV-2 NGC were more susceptible to infection than BALB/c mice, showing increased liver enzymes, extended viremia, dissemination to organs and histological alterations in liver and small intestine. Furthermore, the immune response in DENV-infected C57BL/6 mice exhibited a marked Th1 bias compared to BALB/c mice. These findings highlight the possibility of establishing an immunocompetent mouse model of DENV-2 infection in suckling mice that reproduces certain signs of disease observed in humans and that could be used to further study age-related mechanisms of dengue pathogenesis.
登革热是全球热带和亚热带地区的一个重大公共卫生问题,主要影响儿童。非常年幼的儿童患登革热感染严重表现的风险增加。该人群中登革热疾病的发病机制尚未完全清楚。在这项研究中,我们建立了一种在乳鼠中感染登革病毒的小鼠模型,以研究疾病的发病机制。与 BALB/c 小鼠相比,感染 DENV-2 NGC 的 3 日龄 C57BL/6 小鼠对感染更敏感,表现出肝酶升高、延长的病毒血症、向器官扩散以及肝和小肠的组织学改变。此外,与 BALB/c 小鼠相比,感染 DENV 的 C57BL/6 小鼠的免疫反应表现出明显的 Th1 偏向。这些发现强调了在乳鼠中建立 DENV-2 感染的免疫功能健全的小鼠模型的可能性,该模型可再现人类观察到的某些疾病迹象,并可用于进一步研究与年龄相关的登革热发病机制。