Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore 138648.
J Immunol. 2013 Jun 15;190(12):6295-302. doi: 10.4049/jimmunol.1300304. Epub 2013 May 13.
In recent years, Chikungunya virus (CHIKV) was responsible for epidemic outbreaks in intertropical regions. Although acquired immunity has been shown to be crucial during CHIKV infection in both humans and mice, their exact role in the control of CHIKV infection remains unclear. In this study, wild-type (WT), CD4(-/-), and B cell (μMT) knockout mice were infected with CHIKV. Sera were taken at different days postinfection and measured for anti-CHIKV Ab levels. Isotype and neutralizing capacity of these Abs were assessed in vitro, and specific linear epitopes were mapped. Viremia in CHIKV-infected μMT mice persisted for more than a year, indicating a direct role for B cells in mediating CHIKV clearance. These animals exhibited a more severe disease than WT mice during the acute phase. Characterization of CHIKV-specific Abs revealed that anti-CHIKV Abs were elicited early and targeted epitopes mainly at the C terminus of the virus E2 glycoprotein. Furthermore, CD4(-/-) mice could still control CHIKV infection despite having lower anti-CHIKV Ab levels with reduced neutralizing capacity. Lastly, pre-existing natural Abs in the sera of normal WT mice recognized CHIKV and were able to partially inhibit CHIKV. Taken together, natural and CHIKV infection-induced specific Abs are essential for controlling CHIKV infections.
近年来，基孔肯雅病毒（CHIKV）在热带地区引发了疫情爆发。尽管在人类和小鼠的 CHIKV 感染中，获得性免疫被证明是至关重要的，但它们在控制 CHIKV 感染中的确切作用仍不清楚。在这项研究中，野生型（WT）、CD4（-/-）和 B 细胞（μMT）敲除小鼠感染了 CHIKV。在不同的感染后天数采集血清，并测量抗 CHIKV Ab 水平。在体外评估这些 Abs 的同种型和中和能力，并绘制特异性线性表位。在 CHIKV 感染的 μMT 小鼠中，病毒血症持续了一年多，表明 B 细胞在介导 CHIKV 清除中具有直接作用。这些动物在急性阶段的疾病比 WT 小鼠更为严重。对 CHIKV 特异性 Abs 的表征表明，抗 CHIKV Abs 被早期诱导，并主要针对病毒 E2 糖蛋白的 C 末端靶向表位。此外，尽管 CD4（-/-）小鼠的抗 CHIKV Ab 水平较低，中和能力降低，但仍能控制 CHIKV 感染。最后，正常 WT 小鼠血清中的天然存在的 Abs 识别 CHIKV，并能部分抑制 CHIKV。总之，天然和 CHIKV 感染诱导的特异性 Abs 对于控制 CHIKV 感染是必不可少的。
