Genetics of bacteria-mediated viral co-infection

细菌介导的病毒共感染的遗传学

• 批准号: 9050625
• 负责人: Julie K Pfeiffer
• 金额: $ 20.22万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-10 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9050625
• 关键词: Antibiotics; Antibody Specificity; Bacteria; Bacterial Polysaccharides; Binding; Biological Assay; Cells; Data; DsRed; Electron Microscopy; Enteral; Environment; Evolution; Exposure to; Flow Cytometry; Frequencies; Future; Gastrointestinal tract structure; Genetic; Genetic Recombination; Genome; Health; Human poliovirus; In Vitro; Incubated; Infection; Intestines; Link; Lipopolysaccharides; Mediating; Micelles; Microbe; Modeling; Mouse Mammary Tumor Virus; Mus; Mutation; Norovirus; Oral; Peptidoglycan; Plaque Assay; Polysaccharides; Population; RNA Viruses; Reovirus; Science; Surface; Testing; Thinking; Viral; Virion; Virus; Virus Diseases; Virus Replication; Work; co-infection; fitness; genetic approach; genetic evolution; gut microbiota; in vivo; interest; microbial community; microbiota; mouse model; mutant; novel strategies; particle; research study; screening; transmission process; viral transmission; virology; virus genetics

 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.

 描述（由适用提供）：肠道病毒在哺乳动物消化道中遇到一个庞大的微生物群落。但是，肠道菌群对肠道病毒的影响尚不清楚。使用小鼠模型，表明肠道细菌促进了四种无关肠道病毒的感染：脊髓灰质炎病毒，依索病毒，鼠氯诺如病毒和小鼠乳腺肿瘤病毒。所有这些病毒结合细菌和/或细菌表面多糖，从而增加了细菌可能向宿主细胞传递病毒以启动肠道中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异伏病毒颗粒。由于与哺乳动物肠细胞相比，细菌很小，因此细菌可能会提供一个以上的每个宿主细胞。考虑到有限数量的病毒是传播的，细菌介导的多种病毒传递到肠道细胞很有趣，因此第一个复制周期很可能是在非常低的感染（MOI）下引发的。即使存在很少的病毒，细菌也可能促进病毒共感染。实际上，在体外或体内暴露于细菌后，由于细菌介导的共感染而导致多个创建者产生的杂种斑块产生的杂种斑块产生。这些结果引发了有关我们的MOI和牙菌体形成单元（PFU）的概念的问题 - 什么是传染性单元？由于细菌结合的病毒可能会引发同步共同感染，因此细菌会促进脊髓灰质炎病毒基因组基因组段的基因重组还是重新分类？由于突变和颗粒而导致的许多RNA病毒降低了适应性：PFU比率很高：细菌介导的病毒共同感染是否可以增强病毒复制和进化？在这项工作中，我们将使用脊髓灰质炎病毒和依泊病毒作为遗传障碍模型病毒，以测试细菌介导同步感染的假设，从而促进病毒重组或浮雕，即使存在很少的病毒。这项工作有可能重新定义我们如何看待“病毒感染单元”，这与所有病毒学有关。