Genetics of bacteria-mediated viral co-infection

 描述(申请人提供)：肠道病毒在哺乳动物的消化道中遇到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。在小鼠模型中，研究表明，肠道细菌促进了四种无关的肠道病毒的感染：脊髓灰质炎病毒、呼肠孤病毒、小鼠诺如病毒和小鼠乳腺肿瘤病毒。所有这些病毒都与细菌和/或细菌表面多糖结合，增加了细菌可能将病毒粒子运送到宿主细胞以启动肠道第一个病毒复制周期的可能性。每种细菌结合多个脊髓灰质炎病毒或呼肠孤病毒颗粒。由于细菌与哺乳动物肠道细胞相比较小，细菌可能会在每个宿主细胞上传递不止一个病毒粒子。考虑到有限数量的病毒粒子被传播，因此第一个复制周期可能以极低的感染粒子(MOI)启动，因此细菌介导的多个病毒粒子进入肠道细胞是有趣的。即使在病毒粒子很少的情况下，细菌也可能促进病毒的共同感染。事实上，在体外或体内暴露于细菌后，由于细菌介导的共同感染，基因标记的脊髓灰质炎病毒产生了来自多个创始人的嵌合斑块。这些结果对我们的MOI和斑块形成单位(PFU)的概念提出了质疑--什么是感染单位？由于细菌结合的病毒可能引发同步共感染，细菌是否促进了脊髓灰质炎病毒的基因重组或呼肠孤病毒基因组片段的重新分类？种群中的许多RNA病毒由于突变和颗粒：pfu比率高而降低了适合度：细菌介导的病毒共同感染是否增强了病毒的复制和进化？在这项工作中，我们将使用脊髓灰质炎病毒和呼肠孤病毒作为遗传上可处理的模型病毒，以测试细菌介导同步联合感染的假设，从而促进病毒重组或重组，即使在病毒粒子很少的情况下也是如此。这项工作有可能重新定义我们对“病毒感染单位”的看法，这是与所有病毒学相关的。

 DESCRIPTION (provided by applicant): 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 shown that intestinal bacteria promote infection with four unrelated enteric viruses: poliovirus, reovirus, murine norovirus, and mouse mammary tumor virus. All of these viruses bind bacteria and/or bacterial surface polysaccharides, raising the possibility that bacteria may deliver virions to host cells to initiat the first viral replication cycle in the gut. Each bacterium binds multiple poliovirus or reovirus particles. Since bacteria are small compared to mammalian intestinal cells, a bacterium may deliver more than one virion per host cell. Bacteria-mediated delivery of multiple virions into an intestinal cell is interesting considering that a limited number of virions are transmitted and therefore the first replication cycle is likely initiated at an extremely low multiplicity of infecion (MOI). Bacteria may facilitate viral co-infection even when very few virions are present. Indeed, after exposure to bacteria in vitro or in vivo, genetically marked polioviruses generated chimeric plaques derived from multiple founders due to bacteria-mediated co-infection. These results raise questions about our concepts of MOI and plaque-forming unit (PFU)-what is an infectious unit? Since bacteria-bound viruses may initiate synchronous co-infection, do bacteria promote poliovirus genetic recombination or reassortment of reovirus genome segments? Many RNA viruses within a population have reduced fitness due to mutation and particle:PFU ratios are high: Does bacteria-mediated viral co-infection enhance viral replication and evolution? In this work, we will use poliovirus and reovirus as genetically tractable model viruses to test the hypothesis that bacteria mediate synchronous co-infection and therefore promote viral recombination or reassortment even when very few virions are present. This work has the potential to redefine how we think about "the viral infectious unit", which is relevant for all of virology.