J Virol 2011 Nov;85 (21): 11090-7. [IF:5.189]
Matrix protein-specific IgA antibody inhibits measles virus replication by intracellular neutralization.
Zhou D , Zhang Y , Li Q , Chen Y , He B , Yang J , Tu H , Lei L , Yan H .
Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
武汉大学，中国科学院武汉病毒研究所，病毒学国家重点实验室
Abstract
Measles virus (MV) is still an imposing threat to public health. The matrix (M) protein has been shown not only to function as a structure block in the assembled MV virions, but also to regulate viral RNA synthesis, playing an important role in MV's replication and assembly. In the present study, we generated a panel of IgG monoclonal antibodies (MAbs) against M protein and successfully obtained one IgA MAb (5H7) from the IgG panel. Employing the polarized Vero cells grown in the two-chamber transwell model, we investigated whether M-specific 5H7 IgA MAb could suppress MV's replication and assembly. The data presented indicate that, while failing to show the activities of traditional neutralization and immune exclusion, M-specific IgA MAb was able to effectively inhibit viral replication by intracellular neutralization (78%), supporting the notion that the M protein is important for MV assembly and replication and implying that the M protein was an effective target antigen. The data also showed that MV had a long entry and assembly phase during viral replication, providing an extended window for IgA intervention. The colocalization of M proteins and M-specific 5H7 IgA MAbs demonstrated that the intracellular neutralization was due to the direct binding of the M-specific 5H7 IgA MAbs to the M proteins. In summary, the present study has added another example showing that IgA antibodies targeting internal viral antigens could proactively participate in mucosal immune protection by intracellular neutralization and has provided evidence that M protein might be included as a target antigen in future MV vaccine design.
摘要
麻疹病毒（MV）迄今为止仍然是公众健康的一大威胁。基质（M）蛋白已被证明不仅在MV病毒颗粒组装时发挥功能，而且还能调节病毒RNA的合成，在MV的复制和装配中发挥重要作用。在最近的研究中，我们制作了对抗M蛋白的IgG单克隆抗体（(MAbs）面板，并从IgG面板成功获得IgA MAb (5H7)。采用极化Vero细胞两室联通模型培养细胞，我们研究了M -特定 5H7单克隆抗体IGA是否能抑制MV的复制和装配。所得到的数据表明，虽然未能显示传统中和免疫排斥的活性， M–特定 IgA的单克隆抗体能够通过细胞内中和（78％）有效地抑制病毒复制，支持了即M蛋白对于MV装配和复制是很重要的假设，并暗示M蛋白是一种有效的靶抗原。数据还显示，病毒复制过程中有一个长时间的进入和组装阶段，为IGA介入干预提供了一个扩展窗口。 M蛋白共区域化和M -特定5H7 IGA单克隆抗体表明，细胞内失效是由于M -特定5H7 IGA的单克隆抗体与M蛋白直接结合。总之，目前的研究证明了一个事实：针对内部病毒抗原的IgA抗体可以通过细胞中和作用积极参与粘膜免疫保护，已提供的数据表明M蛋白可能会在未来MV疫苗设计中作为靶抗原。
