Mehlhop Erin, Ansarah-Sobrinho Camilo, Johnson Syd, Engle Michael, Fremont Daved H, Pierson Theodore C, Diamond Michael S
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cell Host Microbe. 2007 Dec 13;2(6):417-26. doi: 10.1016/j.chom.2007.09.015.
Severe dengue virus infection can occur in humans with pre-existing antibodies against the virus. This observation led to the hypothesis that a subneutralizing antibody level in vivo can increase viral burden and cause more severe disease. Indeed, antibody-dependent enhancement of infection (ADE) in vitro has been described for multiple viruses, including the flaviviruses dengue virus and West Nile virus. Here, we demonstrate that the complement component C1q restricts ADE by anti-flavivirus IgG antibodies in an IgG subclass-specific manner in cell culture and in mice. IgG subclasses that avidly bind C1q induced minimal ADE in the presence of C1q. These findings add a layer of complexity for the analysis of humoral immunity and flavivirus infection.
既往感染过登革病毒的人可能会发生严重的登革病毒感染。这一观察结果引发了一个假说，即体内亚中和抗体水平会增加病毒载量并导致更严重的疾病。事实上，包括黄病毒科的登革病毒和西尼罗河病毒在内的多种病毒在体外都有抗体依赖的感染增强（ADE）现象的描述。在此，我们证明补体成分C1q在细胞培养和小鼠体内以IgG亚类特异性方式限制抗黄病毒IgG抗体介导的ADE。在C1q存在的情况下，能与C1q强烈结合的IgG亚类诱导的ADE最小。这些发现为体液免疫和黄病毒感染的分析增添了一层复杂性。
