Sex-dependent replication of coxsackievirus

柯萨奇病毒的性别依赖性复制

• 批准号: 9332385
• 负责人: Christopher Michael Robinson
• 金额: $ 13.6万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9332385
• 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; Intestines; Light; Liver; Meningoencephalitis; Microbe; Modeling; Mouse Mammary Tumor Virus; Mus; Norovirus; Oral; Organ; Pathogenesis; Peripheral; Play; Reoviridae; 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; experimental study; fecal transplantation; gut microbiota; human male; in vivo; insight; male; microbiota; mouse model; oral infection; pathogen; sex; viral myocarditis

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（CVB 3）是一种常见的感染，通过粪便-口腔途径传播。几乎所有的人类 在5岁时感染柯萨奇病毒，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 我发现，与人类相似，雄性小鼠死于CVB 3诱导的疾病，而雌性小鼠则是如此。 没有有趣的是，CVB 3在雄性小鼠肠道中的复制增强，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群时，可以恢复CVB 3的复制 通过粪便移植这第一次表明，肠道细菌的性别差异会改变病毒的传播。 复制的然而，这种性别偏见的机制仍然未知。新的数据表明， 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CVB 3复制在 肠子本研究的目的是鉴定促进CVB 3复制的肠道细菌， 性激素对肠道柯萨奇B3病毒复制的影响。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.