Dengue is one of the most prevalent arthropod-borne viral diseases in humans. There is still no effective vaccine or treatment to date. Previous studies showed that mosquito-derived factors present in saliva or salivary gland extract (SGE) contribute to the pathogenesis of dengue. In this study, we aimed to investigate the interplay between mosquito vector and DENV and to address the question of whether the mosquito vector alters the virus that leads to consequential disease manifestations in the mammalian host. DENV2 cultured in C6/36 cell line (culture-DENV2) was injected to Aedes aegypti intrathoracically. Saliva was collected from infected mosquitoes 7 days later. Exploiting the sensitivity of Stat1-/- mice to low dose of DENV2 delivered intradermally, we showed that DENV2 collected in infected mosquito saliva (msq-DENV2) induced more severe hemorrhage in mice than their culture counterpart. Msq-DENV2 was characterized by smaller particle size, larger plaque size and more rapid growth in mosquito as well as mammalian cell lines compared to culture-DENV2. In addition, msq-DENV2 was more efficient than culture-DENV2 in inducing Tnf mRNA production by mouse macrophage. Together, our results point to the possibility that the mosquito vector provides an environment that alters DENV2 by changing its growth characteristics as well as its potential to cause disease.

中文翻译：

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感染蚊子会改变 DENV-2 特征并增强 Stat1-/- 小鼠的出血诱导潜力。

登革热是人类最普遍的节肢动物传播病毒性疾病之一。迄今为止，仍然没有有效的疫苗或治疗方法。先前的研究表明，唾液或唾液腺提取物 (SGE) 中存在的蚊源性因子有助于登革热的发病机制。在这项研究中，我们旨在调查蚊媒和 DENV 之间的相互作用，并解决蚊媒是否会改变导致哺乳动物宿主继发疾病表现的病毒的问题。在 C6/36 细胞系 (culture-DENV2) 中培养的 DENV2 被注射到埃及伊蚊胸腔内。7 天后从受感染的蚊子中收集唾液。利用 Stat1-/- 小鼠对皮内递送的低剂量 DENV2 的敏感性，我们表明，在受感染的蚊子唾液（msq-DENV2）中收集的 DENV2 比它们的培养物引起了更严重的小鼠出血。与培养-DENV2 相比，Msq-DENV2 的特点是粒径更小，斑块更大，在蚊子和哺乳动物细胞系中生长更快。此外，msq-DENV2 在诱导小鼠巨噬细胞产生 Tnf mRNA 方面比培养物-DENV2 更有效。总之，我们的结果表明，蚊子载体提供了一种环境，通过改变其生长特征以及引起疾病的潜力来改变 DENV2。msq-DENV2 在诱导小鼠巨噬细胞产生 Tnf mRNA 方面比培养-DENV2 更有效。总之，我们的结果表明，蚊子载体提供了一种环境，通过改变其生长特征以及引起疾病的潜力来改变 DENV2。msq-DENV2 在诱导小鼠巨噬细胞产生 Tnf mRNA 方面比培养-DENV2 更有效。总之，我们的结果表明，蚊子载体提供了一种环境，通过改变其生长特征以及引起疾病的潜力来改变 DENV2。