The neutralizing role of IgM during early Chikungunya virus infection.

The neutralizing role of IgM during early Chikungunya virus infection.
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DOI:
10.1371/journal.pone.0171989
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发表时间:
2017
期刊:
影响因子:
3.7
通讯作者:
Chan YF
Chan YF
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chua CL;Sam IC;Chiam CW;Chan YF

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抗体同种型 IgM 比 IgG 更早出现,在症状出现后几天内出现,并且在适应性免疫反应的早期阶段很重要。人们对 IgM 在基孔肯雅病毒 (CHIKV) 感染过程中的功能作用知之甚少,基孔肯雅病毒是一种最近重新出现的虫媒病毒,已在全球范围内引起大规模疫情。在这项研究中,我们研究了马来西亚 CHIKV 爆发期间收集的 102 份血清样本中的抗体反应。我们描述了感染后不同时间 IgM 的中和作用,并检查了感染早期 IgM 和 IgG 对人类免疫血清中和能力的独立贡献,包括中和表位靶标的差异。中和 IgM 早在症状出现的第 4 天就开始出现,并且从第 6 天开始出现与病毒血症的减少有关。 IgM 以与早期 IgG 互补的方式发挥作用,但在第 4 天至第 10 天之间发挥主要中和作用,该作用因个体而异。此后,总中和能力几乎完全归因于强大的中和 IgG 反应。 IgM 优先结合并靶向 CHIKV 表面 E1-E2 糖蛋白上的表位,而不是单个 E1 或 E2。这些发现提供了对 CHIKV 的早期抗体反应的深入了解,并对诊断血清学测定的设计具有影响。
The antibody isotype IgM appears earlier than IgG, within days of onset of symptoms, and is important during the early stages of the adaptive immune response. Little is known about the functional role of IgM during infection with chikungunya virus (CHIKV), a recently reemerging arbovirus that has caused large global outbreaks. In this study, we studied antibody responses in 102 serum samples collected during CHIKV outbreaks in Malaysia. We described the neutralizing role of IgM at different times post-infection and examined the independent contributions of IgM and IgG towards the neutralizing capacity of human immune sera during the early phase of infection, including the differences in targets of neutralizing epitopes. Neutralizing IgM starts to appear as early as day 4 of symptoms, and their appearance from day 6 is associated with a reduction in viremia. IgM acts in a complementary manner with the early IgG, but plays the main neutralizing role up to a point between days 4 and 10 which varies between individuals. After this point, total neutralizing capacity is attributable almost entirely to the robust neutralizing IgG response. IgM preferentially binds and targets epitopes on the CHIKV surface E1-E2 glycoproteins, rather than individual E1 or E2. These findings provide insight into the early antibody responses to CHIKV, and have implications for design of diagnostic serological assays.