MECHANISMS REGULATING AVIAN INFLUENZA VIRUS INFECTIONS IN HUMANS

摘要 禽流感病毒与更严重的疾病有关，但在感染后传播性较低。 比季节性流感病毒对人类的影响更大。单个或小簇的动物模型和有限的研究 人类感染禽流感病例已被用来理解潜在的机制，并取得了不同的成功 推论。在很大程度上阻碍科学进步的是历史上零星的 人类禽流感病例，使比较和广泛的前瞻性研究变得不可行。世界银行的出现 中国体内的H7N9禽流感病毒现在已经改变了这一点。这些H7N9病例与可预测的空间和 时间模式，使得考虑队列研究是可行的。在这里，我们建议进行纵向的 确定人类感染禽流感病毒的免疫学和病毒学特征的研究。我们的研究 将检验两个假设：1)H7N9 AIV引起的严重疾病是缺乏早期交叉感染的结果 保护性CD8+T细胞反应，以及，2)AIV在哺乳动物宿主中的复制限制了病毒种群 分集，这反过来又限制了向前的传输。中国南部是一个特别重要的人类聚居区 禽流感病例是由于其人和家禽密度高所致。我们建议的第一个研究地点 广州医科大学附属医院，也是国家指定参考文献中心 呼吸系统疾病，是非常适合这项研究的。上述目标的实现将导致最大的 到目前为止对人类感染禽流感病毒的全面分析，并与 季节性流感。美国和中国科学家的关键交叉培训也将是一个重要的里程碑 提高全球公共卫生研究能力。

ABSTRACT Avian influenza viruses (AIVs) are associated with more severe disease but less transmissibility after infection of humans than are seasonal influenza viruses. Animal models and limited studies of single or small clusters of AIV human cases have been utilized to understand the underlying mechanisms with varying success and inference. Hampering scientific progress to a substantial degree has been the historically sporadic nature of human AIV cases, making comparative and extensive prospective studies unfeasible. The emergence of the H7N9 AIV in China has now changed this. These H7N9 cases are associated with a predictable spatial and temporal pattern that makes it feasible to consider a cohort study. Here, we propose to conduct a longitudinal study to identify the immunological and virological hallmarks of AIV infections in humans. Our study will test two hypotheses: 1) severe disease caused by H7N9 AIVs is a consequence of a lack of early cross- protective CD8+ T-cell responses, and, 2) replication of AIVs in the mammalian host limits virus population diversity which in turn limits onwards transmission. Southern China is a particularly important region for human cases of AIV due to its high density of humans and domestic poultry. Our proposed study site at the First Affiliated Hospital of Guangzhou Medical University, which is also a designated National Reference Center for Respiratory Diseases, is perfectly suited for this study. The completion of the above aims will lead to the most comprehensive analysis of AIV infections in humans to date and also to a direct side-by-side comparison with seasonal influenza. Critical cross training of US and Chinese scientists will also be a major milestone leading to improved global public health research capacity.