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Sex-dependent replication of coxsackievirus

柯萨奇病毒的性别依赖性复制

基本信息

批准号：
9163498
负责人：
Christopher Michael Robinson
金额：
$ 11.98万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9163498
关键词：
Affect Age Animals Antibiotics Bacteria Binding Brain Cell-Matrix Junction Cells Communities Complex Coxsackie Viruses Coxsackievirus Infections Data Disease Enhancers Enteral Environment Environmental Risk Factor Estrogens Female Foundations Gastrointestinal tract structure Germ-Free Goals Gonadal Steroid Hormones Hand, Foot and Mouth Disease Health Heart Hormones Human Human body Human poliovirus Immune response In Vitro Infection Injection of therapeutic agent Intestinal Hormones Intestines Lead Light Liver Meningoencephalitis Microbe Modeling Mouse Mammary Tumor Virus Mus Norovirus Oral Organ Pathogenesis Peripheral Play Reovirus Role Route Sampling Sex Bias Sex Characteristics Testosterone Time United States Vaccines Viral Viral Pathogenesis Virion Virus Virus Diseases Virus Replication Work deep sequencing density fecal transplantation gut microbiota human male in vivo insight male microbiota mouse model oral infection pathogen research study sex viral myocarditis

项目摘要

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.

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。