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.

 性状（由申请方提供）：肠道病毒在哺乳动物消化道中遇到大量微生物群落。然而，肠道微生物群对肠道病毒的影响还不清楚。使用小鼠模型，显示肠道细菌促进四种不相关的肠道病毒的感染：脊髓灰质炎病毒、呼肠孤病毒、鼠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，提高了细菌可能将病毒体递送到宿主细胞以启动肠道中的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的肠细胞相比很小，因此细菌可以为每个宿主细胞递送一个以上的病毒体。考虑到有限数量的病毒体被传递，因此第一个复制周期可能以极低的感染复数（MOI）开始，细菌介导的将多个病毒体递送到肠细胞中是令人感兴趣的。细菌可能会促进病毒的共同感染，即使当很少的病毒体存在。事实上，在体外或体内暴露于细菌后，由于细菌介导的共感染，遗传标记的脊髓灰质炎病毒产生源自多个创始人的嵌合噬斑。这些结果对我们的MOI和噬菌斑形成单位（PFU）概念提出了疑问-什么是感染单位？既然细菌结合的病毒可以启动同步的合并感染，细菌是否促进脊髓灰质炎病毒基因重组或呼肠孤病毒基因组片段的重配？由于突变和粒子：PFU比率高，群体中的许多RNA病毒的适应性降低：细菌介导的病毒共感染是否会增强病毒的复制和进化？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易于处理的模型病毒来测试细菌介导同步共感染的假设，因此即使在病毒体非常少的情况下也能促进病毒重组或重配。这项工作有可能重新定义我们如何看待“病毒感染单位”，这与所有病毒学有关。