Enteric virus-microbiota interactions

项目总结 肠道病毒在哺乳动物的消化道中遇到了一个巨大的微生物群落。然而， 肠道微生物区系对肠道病毒的影响还不是很清楚。使用小鼠模型，它是 最近研究表明，肠道细菌可促进感染三种无关的肠道病毒：脊髓灰质炎病毒、 呼肠孤病毒和小鼠乳腺肿瘤病毒。这些病毒在体内的增强复制和致病机制 含有微生物的小鼠可能通过对宿主和/或病毒的微生物依赖作用而发生。对于 模型脊髓灰质炎病毒，数据表明细菌产品直接与病毒颗粒和 增加病毒的传染性。具体地说，细菌表面多糖，如脂多糖和 肽聚糖，通过增强病毒粒子的稳定性和帮助附着到宿主细胞来增强脊髓灰质炎病毒的感染力。 然而，多糖介导的病毒感染力增强的确切机制仍不清楚。 同样，相互作用和随后的感染力增强所需的病毒粒子和多糖特性 都不清楚。通过了解微生物区系介导的病毒粒子感染力增强的具体机制， 新的抗病毒方法是可能的。这项工作的目标是确定病毒粒子和多糖 相互作用和提高感染力的要求，并检查细菌和 细菌表面多糖增强脊髓灰质炎病毒和泰勒氏小鼠脑炎的病毒感染性 病毒作为易于处理的小核糖核酸病毒模型。这将通过四个具体目标来实现：1.确定 微生物区系/多糖作用所需的脊髓灰质炎病毒粒子特性，2.定义多糖特性 与脊髓灰质炎病毒相互作用所需，3.研究多糖增强作用的机制 脊髓灰质炎病毒的传染性，以及4.检查微生物区系对另一种小核糖核酸病毒--泰勒氏小鼠脑炎的影响 病毒(TMEV)。肠道微生物区系很可能使多种肠道病毒受益。总体而言，肠道 病毒可能已经进化出一种机制，将肠道微生物作为环境传感器来启动复制 在肠道的最佳位置。了解为什么肠道病毒需要肠道细菌可能会提供信息 限制肠道病毒感染的抗病毒和疫苗战略。

Project summary Enteric viruses encounter a vast microbial community in the mammalian digestive tract. However, the effect of the intestinal microbiota on enteric viruses is not well understood. Using mouse models, it was recently shown that intestinal bacteria promote infection with three unrelated enteric viruses, poliovirus, reovirus, and mouse mammary tumor virus. The enhanced replication and pathogenesis of these viruses in microbe-containing mice could occur through microbe-dependent effects on the host and/or virus. For the model picornavirus poliovirus, data suggest that bacterial products directly interact with virus particles and increase viral infectivity. Specifically, bacterial surface polysaccharides, such as lipopolysaccharide and peptidoglycan, enhance poliovirus infectivity by enhancing virion stability and aiding attachment to host cells. However, the precise mechanism of polysaccharide-mediated viral infectivity enhancement remains unknown. Similarly, virion and polysaccharide properties required for interaction and subsequent infectivity enhancement are unclear. By understanding specific mechanisms of microbiota-mediated virion infectivity enhancement, novel antiviral approaches are possible. The goal of this work is to define the virion and polysaccharide requirements for interaction and infectivity enhancement, and to examine mechanisms by which bacteria and bacterial surface polysaccharides enhance viral infectivity using poliovirus and Theiler's murine encephalitis virus as tractable picornavirus models. This will be accomplished through four specific aims: 1. Identify poliovirus virion properties required for microbiota/polysaccharide effects, 2. Define polysaccharide properties required for interaction with poliovirus, 3. Examine the mechanism by which polysaccharides enhance poliovirus infectivity, and 4. Examine microbiota effects on another picornavirus, Theiler's murine encephalitis virus (TMEV). It is likely that multiple enteric viruses benefit from the intestinal microbiota. Overall, enteric viruses may have evolved mechanisms to use gut microbes as an environmental sensor to initiate replication at the optimal site in the intestine. Understanding why enteric viruses require intestinal bacteria may inform antiviral and vaccine strategies to limit enteric virus infections.