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：
10444388
负责人：
Christopher Michael Robinson
金额：
$ 6.8万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
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 2022-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10444388
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 Injections Intestines Light Liver Meningoencephalitis Microbe Modeling Mouse Mammary Tumor Virus Mus Norovirus Oral Organ Pathogenesis Peripheral Play Reovirus Role Route Sampling Sex Bias Sex Differences Testosterone Time United States Vaccines Viral Viral Pathogenesis Virion Virus Virus Diseases Virus Replication Work deep sequencing density enteric infection enteric virus infection experimental study fecal transplantation gut microbiota human male human pathogen in vivo insight male microbiota mouse model oral infection 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.

项目概要柯萨奇病毒 B3 (CVB3) 是一种通过粪口途径传播的常见感染。几乎所有人类 5岁时感染柯萨奇病毒，柯萨奇病毒是病毒性心肌炎的主要原因，脑膜脑炎、手足口病。使用最近开发的小鼠模型进行研究 CVB3，我发现，与人类类似，雄性小鼠会死于 CVB3 诱导的疾病，而雌性小鼠则会死于 CVB3 引起的疾病不是。有趣的是，CVB3 在雄性小鼠肠道中的复制得到增强，并且需要肠道细菌。此外，当给予雄性小鼠的微生物群时，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改变了病毒复制。然而，这种性别偏见的机制仍然未知。新数据表明，肠道男性和女性的细菌不同，细菌差异与性激素相关，例如睾酮。这些数据表明，细菌和性激素可能会影响 CVB3 的复制。肠。本研究的目的是鉴定促进 CVB3 复制的肠道细菌并研究性激素对肠道 CVB3 复制的影响。这些研究将为我们提供重要的见解柯萨奇病毒复制所需的肠道环境将有助于了解人类感染。