Synergism Between Influenza Virus and Pneumococcus

流感病毒与肺炎球菌之间的协同作用

• 批准号: 6957297
• 负责人: JONATHAN A MCCULLERS
• 金额: $ 31.88万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6957297
• 关键词: Orthomyxoviridae; Streptococcus pneumoniae; bacteria infection mechanism; bacterial pneumonia; cell line; gene expression; genetically modified animals; glycosylation; host organism interaction; interleukin 10; laboratory mouse; macrophage inflammatory proteins; microorganism immunology; microorganism interaction; point mutation; secondary infection; toll like receptor; transforming growth factors; virulence; virus protein

DESCRIPTION (provided by applicant): Influenza and pneumonia together account for more than 36,000 deaths and 114,000 hospitalizations annually in the United States. Despite the availability of an excellent healthcare system and effective antimicrobials directed against both influenza and bacterial causes of pneumonia, a substantial number of these deaths are due to secondary bacterial pneumonia. The molecular mechanisms that underlie the interaction between respiratory viruses and bacteria are largely unknown. Since secondary bacterial infections account for a significant proportion of the deaths that occur during circulation of virulent strains, it is critical that we understand the basis of this synergy before the next highly pathogenic influenza virus enters the population from avian sources or as a result of bioterrorism. This application proposes in vitro and in vivo experiments to study this interaction utilizing an animal model of synergism between influenza virus and Streptococcus pneumoniae developed in the laboratory of the Principal Investigator. The main hypotheses that will be tested are that strain-specific influenza virulence factors cause alterations of innate immunity of the host that allow pneumococcal strains expressing particular proteins to survive and produce disease. A detailed understanding of this interaction will provide information important for surveillance and control of influenza viruses, as well as support for drug and vaccine based interventions aimed at amelioration of human disease and death caused by bacterial superinfection following respiratory viral disease. More broadly, the proposed work addresses an interesting biological question, that of polymicrobial interactions, and should serve as a model and stimulus for investigation of the contribution of multiple organisms to other disease states.

描述（由申请人提供）：在美国，流感和肺炎共同占36,000多人的死亡和114,000例住院。尽管有出色的医疗系统和针对肺炎流感和细菌原因的有效抗菌药物，但这些死亡中有很大一部分是由于继发性细菌性肺炎引起的。呼吸病毒与细菌之间相互作用的基础的分子机制在很大程度上尚不清楚。由于继发性细菌感染构成了在有毒菌株循环过程中发生的很大一部分死亡，因此至关重要的是，我们必须在下一个高度致病的流感病毒从禽类来源或生物恐怖主义的结果​​之前理解这种协同作用的基础。该应用建议在体外和体内实验研究这种相互作用，利用流感病毒和肺炎链球菌在主要研究者实验室中开发的协同模型。将要测试的主要假设是菌株特异性的流感毒力因子会导致宿主先天免疫的改变，从而允许表达特定蛋白质的肺炎球菌菌株生存并产生疾病。对这种相互作用的详细理解将为对流感病毒的监测和控制重要，以及对旨在改善人类疾病的药物和疫苗干预措施的支持，并在呼吸道病毒疾病后由细菌次感染引起的死亡。更广泛地说，拟议的工作解决了一个有趣的生物学问题，即多生物相互作用，应作为研究多种生物对其他疾病状态的贡献的模型和刺激。