Enteric virus-microbiota interactions

通过粪便-口腔途径传播的病毒是最常见的人类感染之一，但人们知之甚少。 关于影响肠道传播和病毒复制的因素。胃肠道是一种 复杂的环境和肠道病毒会遇到一个巨大的微生物群落。肠道细菌促进 肠道病毒在小鼠体内的复制和致病机制，包括脊髓灰质炎病毒、呼肠孤病毒、小鼠乳腺肿瘤 病毒和诺如病毒。因此，来自四个家族的无关病毒受益于肠道细菌，突出了 了解病毒-微生物区系相互作用的重要性。微生物区系促进肠道病毒复制 通过多种机制，包括与病毒颗粒的直接相互作用，帮助附着和稳定， 间接调节宿主的先天免疫反应。虽然脊髓灰质炎病毒和柯萨奇病毒B3 (CVB3)是短小航病科家族中两个密切相关的病毒，我们的数据表明微生物群增强了 他们通过不同的机制感染。虽然抑制脊髓灰质炎病毒复制需要一种有效的鸡尾酒 在四种抗生素中，CVB3的复制被更微妙的抗生素方案所抑制。这些结果表明 CVB3比脊髓灰质炎病毒更依赖微生物区系，可能需要特定的细菌亚群 用于有效的CVB3感染。结肠中的细菌发酵膳食纤维产生短链脂肪酸 (单链脂肪酸)包括醋酸盐、丙酸盐和丁酸盐。单链脂肪酸是地球上最丰富的分子之一。 并以可能影响肠道代谢和基因表达的方式 肠道病毒复制。最近，我们确定一种单一的细菌代谢物丁酸盐足以 促进微生物区系耗竭小鼠的CVB3复制。我们的中心假设是细菌衍生的单链脂肪酸 通过改变宿主基因表达和肠道内环境平衡促进肠道病毒复制。在这项工作中，我们 将1.检查SCFA介导的肠道病毒复制的特异性和2.检查如何 SCFA介导的宿主基因表达变化影响肠道病毒复制。总体而言，我们的目标是使用 模型病毒了解细菌促进肠道病毒感染的机制的能力。

Viruses transmitted by the fecal-oral route are among the most common human infections, but little is known about factors that influence transmission and viral replication in the intestine. The gastrointestinal tract is a complex environment and enteric viruses encounter a vast microbial community. Intestinal bacteria promote replication and pathogenesis of enteric viruses in mice, including poliovirus, reovirus, mouse mammary tumor virus, and norovirus. Thus, unrelated viruses from four families benefit from intestinal bacteria, highlighting the importance of understanding virus-microbiota interactions. Microbiota promote replication of enteric viruses through multiple mechanisms, including direct interactions with viral particles that aid attachment and stability, and indirect modulation of the host innate immune response. Although poliovirus and coxsackievirus B3 (CVB3) are two closely related viruses in the Picornaviridae family, our data suggest that microbiota enhance their infection through distinct mechanisms. While inhibition of poliovirus replication requires a potent cocktail of four antibiotics, CVB3 replication is inhibited by much more subtle antibiotic regimens. These results suggest that CVB3 is more reliant on microbiota than poliovirus and that a specific subset of bacteria may be required for efficient CVB3 infection. Bacteria in the colon ferment dietary fiber to produce short-chain fatty acids (SCFAs) including acetate, propionate, and butyrate. SCFAs are among the most abundant molecules in the distal gastrointestinal tract and influence intestinal metabolism and gene expression in ways that could impact enteric virus replication. Recently, we determined that a single bacterial metabolite, butyrate, is sufficient to promote CVB3 replication in microbiota-depleted mice. Our central hypothesis is that bacteria-derived SCFAs promote enteric virus replication by altering host gene expression and intestinal homeostasis. In this work we will 1. Examine the specificity of SCFA-mediated effects on enteric virus replication and 2. Examine how SCFA-mediated changes in host gene expression affect enteric virus replication. Overall, our goal is to use the power of model viruses to understand mechanisms by which bacteria promote enteric virus infection.