EAGER: Biophysical Study of Solution Behavior and Vulnerability of Viruses with Complex N-glycans

历史上的黑人学院和大学本科项目(HBCU-UP)为加强HBCU的STEM本科教育和研究提供了支持。病毒似乎会根据传播途径中的溶解条件改变其聚集状态。该项目旨在确定病毒糖基化普遍决定溶液状态的程度。由于病毒的传染性、免疫隐蔽性和传播性随着聚集而变化，我们的目标是根据病毒溶液状态的敏感性来确定是否可以额外拦截像流感这样的高度变异病毒。该项目的更广泛影响是更好地了解不同人群解决方案条件的差异在病毒传播方面的差异。虽然人们对这些病毒糖是如何被免疫系统的蛋白质和信号通路识别的很感兴趣，但关于这些糖的生物物理如何从根本上和广泛地保护病毒传播和感染的双重目的，人们知之甚少。该项目有两个目标：1)研究复杂N-聚糖是否广泛地决定病毒在不同溶液条件下的聚集状态，以及病毒的传染性、抗体抵抗力和粘蛋白结合；2)确定甲型流感病毒表面分别具有唾液酸裂解和结合特性的NA和HB外壳蛋白如何系统地改变甲型流感病毒的溶液行为和脆弱性，以适应其毒力需要。方法包括动态光散射、原子力显微镜、荧光显微镜、流变学和细胞培养。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The Historically Black Colleges and Universities - Undergraduate Program (HBCU-UP) provides support to strengthen STEM undergraduate education and research at HBCUs. Viruses appear to change their aggregation state depending on the solution conditions in the transmission pathway. This project is designed to determine the extent to which the solution state is universally determined by the virus glycosylation. Since virus infectivity, immune-stealth, and transmissibility changes with aggregation, our goal is to determine if highly mutable viruses like influenza can be additionally intercepted based on the susceptibility of their solution state. The broader impact of the project is to better understand disparities in virus transmission from differences in the solution conditions in different populations. While there has been a lot of interest in how these virus sugars are recognized by proteins of the immune system and signaling pathways, little is known about how the biophysics of the sugars fundamentally and broadly protects viruses in their twin purposes of transmission and infection. This project has two goals: 1) To investigate if complex N-glycans broadly determine virus aggregation state of viruses, and the infectivity, antibody (Ab) resistance, mucin binding in different solution conditions; and 2) To determine how NA and Hb envelop proteins on influenza A virus, which have Sialic acid -cleaving and -binding properties, respectively, systematically change the solution behavior and vulnerability of Influenza A virus to suits its virulence needs. Methodologies include dynamic light scattering, atomic force microscopy, florescence microscopy, rheology, and cell culture.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.