Outcomes of the Interactions of Flaviviruses with Antibo

黄病毒是一组正链RNA病毒，由于其广泛分布和在人类和经济上重要的家畜中引起疾病的能力而具有全球影响。这一群体中的一些成员，如登革热病毒和西尼罗河病毒，被认为是新出现或再出现的病原体，因为它们与人类接触并引起疾病的发病率每年都在以惊人的速度增加。因此，迫切需要研制和实施安全有效的疫苗和疗法。存在于黄病毒病毒粒子表面的包膜蛋白是自然感染期间体液（抗体介导）免疫反应的主要目标。因此，产生能够结合这一系列病毒蛋白并阻断感染的抗体是免疫反应的一个关键方面，也是疫苗开发的一个重要目标。然而，在某些情况下，抗体的存在也会增加病毒感染的效率。重要的是，这种感染的抗体依赖性增强（ADE）与DEN感染（登革出血热；DHF）更严重的临床结果有关。免疫可能引发能够增强感染的抗体，这一可能性对DEN疫苗的开发提出了重大挑战，并强调了不仅要了解疫苗接种后体液免疫的大小，而且要了解其广度、特异性和持久性的重要性。在这方面，我们正在研究抗体介导的中和和ADE的机制，目的是了解决定黄病毒颗粒与抗体相互作用结果的生化和细胞因素。

Flaviviruses are a group of positive-stranded RNA viruses that have a global impact due to their widespread distribution and ability to cause disease in humans and economically important domesticated animals. Several members of this group, such as dengue virus (DEN) and West Nile virus (WNV), are considered emerging or re-emerging pathogens because the incidence with which they encounter humans and cause disease is increasing each year at an alarming rate. Thus, an urgent need exists for the development and implementation of safe and efficacious vaccines and therapies. The envelope proteins present on the surface of flavivirus virions are the primary targets for the humoral (antibody-mediated) immune response during natural infection. Thus, the generation of antibodies capable of binding to this array of viral proteins and blocking infection is a critical aspect of the immune response, and an important goal of vaccine development. However, under some circumstances, the presence of antibodies can also increase the efficiency of viral infection. Importantly, this antibody-dependent enhancement (ADE) of infection has been linked to a more severe clinical outcome of DEN infection (Dengue hemorrhagic fever; DHF). The possibility that immunization may elicit antibodies capable of enhancing infection poses a significant challenge for the development of a DEN vaccine, and highlights the importance of understanding not only the magnitude, but also the breadth, specificity, and persistence of humoral immunity following vaccination. In this regard, we are investigating the mechanisms of antibody-mediated neutralization and ADE with the goal of understanding the biochemical and cellular factors that determine the outcome of the interaction of flavivirus particles with antibody.