Sex-dependent replication of coxsackievirus

项目摘要 柯萨奇病毒B3(CVB3)是一种常见的传染病，通过粪便-口腔途径传播。几乎所有的人类 在5岁之前感染柯萨奇病毒，而柯萨奇病毒是病毒性心肌炎的主要原因， 脑膜脑炎和手足口病。使用最近开发的小鼠模型来研究 CVB3，我发现，与人类相似，雄性小鼠会死于CVB3诱导的疾病，而雌性小鼠则会 不。有趣的是，雄性小鼠肠道中的CVB3复制增强，需要肠道细菌。 此外，当给予雌性小鼠来自雄性小鼠的微生物区系时，雌性小鼠的CVB3复制可以恢复 通过粪便移植。这首次表明，肠道细菌的性别差异会改变病毒 复制。然而，这种性别偏见的机制仍然不清楚。新出现的数据表明，肠道 细菌在男性和女性中是不同的，细菌的差异与性激素有关，例如 睾丸激素。这些数据表明，细菌和性激素可能会影响CVB3的复制。 肠子。本研究的目的是确定促进CVB3复制的肠道细菌，并研究 性激素对肠道CVB3复制的影响这些研究将对 柯萨奇病毒复制所需的肠道环境，将有利于了解人类 感染。

Project Summary Coxsackievirus B3 (CVB3) is a common infection that is spread by the fecal-oral route. Nearly all humans are infected with a coxsackievirus by the age of 5, and coxsackievirus is a major cause viral myocarditis, meningoencephalitis, and hand, foot, and mouth disease. Using a recently developed mouse model to study CVB3, I found that, similar to humans, male mice succumb to CVB3-induced disease, whereas female mice do not. Intriguingly, CVB3 replication in the intestine of male mice is enhanced and requires intestinal bacteria. Furthermore, CVB3 replication can be restored in female mice when they are given microbiota from male mice by fecal transplantation. This suggests, for the first time, that sex differences in intestinal bacteria alter viral replication. However, the mechanisms for this sex-bias remain unknown. Emerging data indicate that intestinal bacteria differ in males and females and that bacterial differences correlate with sex hormones, such as testosterone. These data suggest that bacteria and sex hormones may influence CVB3 replication in the intestine. The goal of this study is to identify intestinal bacteria that promote CVB3 replication and investigate the effect of sex hormones on intestinal CVB3 replication. These studies will shed significant insights into the intestinal environment required for coxsackievirus replication and will be beneficial to understanding human infections.